Repetitive Transcranial Magnetic Stimulation (Rtms) increases Plasma Calcium both in-vivo and in-vitro
Received Date: Jul 18, 2014 / Accepted Date: Aug 14, 2014 / Published Date: Aug 16, 2014
Background: We have previously demonstrated that brain levels of gamma-aminobutyric acid (GABA) were diminished in patients with various types of dysgeusia and dysosmia by use of magnetic resonance spectroscopy (MRS). We also demonstrated by use of functional magnetic resonance imaging (fMRI) of brain that when these patients were requested to think of their dysgeusia or dysosmia they exhibited significant brain activation in specific brain regions. Treatment with repetitive transcranial magnetic stimulation (rTMS) increased brain levels of GABA as measured by MRS and decreased brain activation as measured by fMRI. These changes were accompanied by increased levels of plasma, erythrocyte and saliva zinc and copper after rTMS.
Purpose: To evaluate if changes in plasma calcium, either in vivo or in vitro, also occurred in these patients after rTMS.
Methods: Measurements of plasma calcium, in vivo and in vitro, were measured in 129 patients with dysgeusia and dysosmia before and after rTMS.
Results: Both in vivo and in vitro levels of plasma calcium increased significantly after rTMS although levels in vivo were higher than in vitro. These changes occurred in both men and women.
Conclusions: These results, as in previous studies with zinc and copper, indicate that electromagnetic fields increase calcium levels. These studies are the first which describe increased levels of plasma calcium both in vivo and in vitro in humans treated with rTMS. These changes are consistent with changes in neuroplasticity that relate to the role that rTMS plays in calcium metabolism related to changes in GABA and other neurotransmitters.
Keywords: Transcranial magnetic stimulation; Calcium; Dysgeusia; Dysosmia; Neuroplasticit
Patients with dysgeusia and dysosmia (distortions of taste and smell, respectively) of several types exhibit significant activation in specific brain regions when measured by functional magnetic resonance imaging (fMRI) of brain . Evaluation of this activation by use of magnetic resonance spectroscopy (MRS) revealed that while this brain activation was extremely robust and widespread  levels of the inhibitory transmitter gamma-aminobutyric acid (GABA) were significantly diminished . Treatment which increased these low levels of brain GABA with either GABAergic drugs  or repetitive transcranial magnetic stimulation (rTMS) of brain  inhibited these sensory distortions [2,3] inhibited the robust activation previously measured in the untreated state using fMRI  and inhibited the dysgeusia and dysosmia . These events were related to effects of rTMS on neuroplasticity .
Transcranial magnetic stimulation (TMS) has been reported to influence several neurotransmitters and neuroactive substances including dopamine [6-11], biogenic amines [12-14], serotonin [15-17], GABA [18-20], 5-HIAA  and interactions among these moieties [7,14]. rTMS has been reported to modify central nervous system excitability [11,22-26], to enhance sensory function , to alter cognition [28-32] and to alter concentrations of several neurotransmitters, as noted above. TMS has also been reported to be useful in several neurological conditions including rehabilitation after ischemic stroke [33,34], decreasing some symptoms of Parkinson’s disease [35,36], improving auditory hallucinations in patients with schizophrenia in some [37,38] but not in other studies  and inhibiting tinnitus [19,40]. In a prior study we demonstrated that rTMS improved taste and smell dysfunction through a putative role in modulating central nervous system plasticity [3-5,41].
In an effort to understand more about the biochemical changes which might relate to these dramatic neurological changes we evaluated changes in plasma, erythrocyte and saliva zinc and copper, in erythrocyte carbonic anhydrase I, II and in the neurotransmitter carbonic anhydrase VI in saliva after rTMS . Results of these studies demonstrated that after rTMS was used in patients with dysgeusia and dysosmia levels of their plasma, erythrocyte and saliva zinc and copper, erythrocyte carbonic anhydrase (CA) I, II and saliva CA VI increased .
Further analysis of these and similar studies revealed that changes in plasma calcium accompanied these changes in zinc, copper and CA. While we had no prior indication that changes in plasma calcium might be related to treatment with rTMS we now present studies in which rTMS increased plasma calcium levels both in vivo and in vitro in patients with various types of dysgeusia and dysosmia.
This was a prospective sham controlled, fixed sequence, open clinical trial conducted between June, 1999 and January, 2014. Changes in sensory acuity, distortions, and plasma calcium before and after rTMS were measured. This study was approved by the IRB of the George Washington University Medical Center.
One hundred and twenty-nine patients, 55 men, aged 40-74y (58 ± 7 y, M ± SEM), 74 women, aged 30-76 y (51 ± 5 y) were studied at The Taste and Smell Clinic (The Clinic) and at the Department of Neurology at the George Washington University Medical Center, both in Washington, DC. Each patient had mild to severe dysgeusia and dysosmia which was characterized by persistent birhinal phantosmia (a distorted odor in the nose in the absence of any external odor [1,3,43]) and/or global oral phantageusia (a distorted taste in the mouth in the absence of any oral stimulus [43,44]), aliageusia (a distorted taste associated with intake of any food or drink [43,44]) and/or aliosmia (a distorted smell associated with the presence of any external odor ) which were profound and interfered with normal life pursuits. Each patient also had mild to severe persistent hyposmia (smell loss as measured by olfactometry ) and hypogeusia (taste loss as measured by gustometry ). Prior to this study sensory distortions persisted for 3 mo to 30 y (3.7±2 y); taste and/or smell loss persisted for 6 mo to 30 y (4.1±2y). Etiologies which initiated these symptoms were head injury  (30 patients), post influenza-like infection (PIHH ) (54 patients), idiopathic causes  (30 patients) and drug reactions  (15 patients). Each patient who presented to The Clinic with these symptoms was treated with rTMS. All studies were consistent with the protocol approved by the IRB of the George Washington University Medical Center to which all patients agreed.
None had either clinical otolaryngological or neurological symptoms other than loss of sensory acuity and presence of sensory distortions. None had any psychiatric symptom other than some depression associated with persistence of these sensory impairments. Physical examination of each patient including examination of the head and neck and general neurological examination was within normal limits. Both anatomical brain MRI and electroencephalograms were within normal limits.
An entire battery of sensory measurements (olfactometry and gustometry as identified above ) was obtained at the initial patient visit to The Clinic and repeated immediately prior to and after rTMS. Each test battery and rTMS trial  was performed independent of knowledge of any prior result.
rTMS was performed with a Cadwell (Kennewick, WA) magneto-electric stimulator MES-10 monitored by a TECA TD20 (Pleasantville, NY) wave form generator. Stimulation was applied by use of a single circular 5 cm (internal diameter) coil .
Three consecutive stimulation procedures were used at each rTMS trial . The first two were sham procedures, the third was the real trial. Each procedure consisted of the patient viewing the stimulating instrument and, with each activation and disappearance of the signal, visualizing the on and off appearance of a green light and hearing on and off sound of the activity stimulus click.
Prior to this procedure blood was obtained by venipuncture and placed into each of two acid washed glass tubes containing 100 µl heparin. One tube was centrifuged at 3000xg for 10-15 min. The plasma contents of this tube were aspirated and saved at 4°C for measurements of plasma calcium. The contents of the second tube were placed in ice and treated with rTMS in vitro as noted below.
The first rTMS procedure was a sham procedure consisting of applying 20 stimuli at intervals of 1-5 sec at 25-35% maximal output [25-35% of 1.5T or ~0.3-0.5T (since stimulus delivery was non-linear)] sequentially (a) to the anterior right shoulder, [at the lateral acromial process of the clavicle (near Erb’s point)] then (b) anterior left shoulder (near Erb’s point) and then (c) to the back of the mid neck region (at the level of C5-8 at 30-40% maximal output or ~0.4-0.8T); mild to moderate muscle group flexion of arm and hand muscles (shoulder stimulation) and neck, strap and facial muscles (neck stimulation), respectively, followed stimulation at each respective site and was visually monitored .
The second rTMS procedure was another sham procedure consisting of applying 20 stimuli at intervals of 1-5 sec at 10-15% maximal output (10-15% of 1.5T or ~0.08-0.15T, a subthreshold stimulus) sequentially to four skull regions in a fixed sequence (left temporoparietal, occipital, right frontoparietal, frontal). No subjective or peripheral muscle response occurred in response to this stimulation .
The third rTMS procedure was the real trial consisting of applying 20 stimuli at intervals of 1-5 sec at 40-55% maximal output (~0.8-1.1T) sequentially to each skull location as in the second sham procedure noted above. Right/left thenar and/or phalangeal flexion after left/right temporoparietal stimulation, respectively, occurred and was monitored by visual observation. Mild facial muscle flexion usually occurred after occipital stimulation and bilateral eye blinking usually occurred after frontal stimulation .
After this third procedure venipuncture was again performed, the blood transferred to another acid washed glass tube containing 100 µl heparin, centrifuged at 3000xg in a refrigerated centrifuge for 10-15 min, the plasma removed and stored at 4ºC until assayed. This sample was labeled the in vivo plasma sample. At this time, the second tube previously obtained was treated with direct application of the same rTMS procedure applied to one of the skull regions noted above in the third rTMS procedure. This consisted of applying 20 stimuli at intervals of 1-5 sec at 40-55% of maximal output directly to the top of the tube as it was placed in an ice bath. After this stimulation this tube was centrifuged at 3000xg in a refrigerated centrifuge for 10-15 min, the plasma aspirated and stored at 4ºC to be assayed. This sample was labeled in vitro sample and all in vitro results relate to measurements obtained using this plasma sample.
Plasma from each of the three tubes was analyzed by flame aspiration atomic absorption spectrophotometry (AAS) on a Thermo Jarrell Ash AAS modified by the Maxwell Instrumentation Company (Salisbury, NC) by a variation of the method previously developed for measurement of zinc and copper  and approved and monitored by the Clinical Laboratory Improvement Amendments (CLIA) of the U.S. government.
All studies were performed independent of any knowledge of the treatment condition of any patient. Since each patient had collection of plasma performed before rTMS and after both in vitro and in vivo rTMS treatment paired comparisons of analysis were performed for each patient group with results considered significant using Student’s t-test with p<0.05.
Significant increases in plasma calcium occurred after rTMS both in vivo and in vitro (Table 1). In vivo levels were about 10% higher than in vitro levels.
|Condition||Plasma calcium (mg/dl)|
|rTMS Irradiation (in vitro)||9.35±0.04a|
|Post rTMS (in vivo)||9.39±0.04b|
|With respect to Pre rTMS (by paired comparison): a p<0.01; b p<0.05
Table 1: In vivo and in vitro changes in plasma calcium before and after rtms in 129 atients with dysgeusia and dysosmia.
When analyzed by gender, increases in plasma calcium occurred after rTMS in both in vivo and in vitro studies although increases were significant only for men after in vivo rTMS (Table 2). There were no significant differences under any condition in plasma calcium between men and women.
|Condition||Plasma calcium (mg/dl)|
|Pre rTMS (in vivo)|
|rTMS Irradiation (in vitro)|
|Post rTMS (in vivo)|
|With respect to Pre rTMS (by paired comparison): b p<0.05 * Mean±SEM|
Table 2: In vivo and in vitro changes in plasma calcium before and after rtms in 55 men and 4 women with dysgeusia and dysosmia.
When analyzed by age, increases in plasma calcium occurred after rTMS in both in vivo and in vitro studies although levels were generally not significantly increased except for comparisons of in vivo studies pre and post rTMS in the 31-50 y age group (Table 3).
|Condition||Plasma calcium (mg/dl)|
|Pre rTMS[in vivo]|
|10-30 years (4)||9.50±0.13*|
|31-50 years (18)|
|51-70 years (75)9.30±0.05|
|71-90 years (32)||9.26±0.09|
|rTMS Irradiation [in vitro]|
|10-30 years (4)||9.78±0.09|
|31-50 years (18)||9.39±0.09|
|51-70 years (75)||9.33±0.05|
|71-90 years (32)||9.34±0.10|
|Post rTMS[in vivo]|
|10-30 years (4)||9.73±0.11|
|31-50 years (18)||9.51±0.10b|
|51-70 years (75)||9.36±0.06|
|71-90 years (32)||9.33±0.09|
|With respect to Pre rTMS (by paired comparison): b p<0.05 * Mean±SEM; () Number of patients|
Table 3: In vivo and in vitro changes in plasma calcium before and after rtms in patients with dysgeusia and dysosmia characterized by age.
It is of interest that increased plasma calcium occurred after both in vivo and in vitro studies with use of rTMS. The mechanism(s) by which these changes occurred are complex. In vitro studies involved rTMS treatment of whole blood by which cellular calcium was evidently released into the plasma. Previous studies have demonstrated that pulsed magnetic field effected calcium dependent function in several tissues  with several studies demonstrating that low energy electromagnetic fields (EMF) elicit changes in calcium levels [51-55]. EMF increases net calcium flux in rat lymphocytes [53,54] with increased free calcium derived from human T-cells . Magnetic fields have been shown to influence molecular events in signal transduction in T cells in which intracellular calcium is involved .
On the other hand, in vivo studies involved increased plasma calcium as a result of rTMS stimulation to patients at specific brain regions. These results are consistent with the changes elicited by application of EMF to human astrocytoma cells , increasing net calcium flux and cytosolic calcium concentrations in osteoplast-like cells , in human hepatoma cells  and in magnetic field effects on calcium fluxes which inhibited apoptosis in human glioblastoma cells . Although all studies did not demonstrate these effects [57,58] the present studies and many others indicate that calcium is involved in mediation of field effects which can also involve the immune system .
The neurological effects we have demonstrated after brain application of rTMS in these in vivo studies have been associated with significant increases in brain GABA [2,3] which enhanced neuroplasticity. Magnetic fields have also been shown to enhance neuronal calcium dynamics which has been considered to play an important role in induction and maintenance of neuroplasticity . Even minor changes in calcium regulation can alter nervous system activity . These changes have also been associated with effects of calcium on the signal transduction cascade  not only on brain GABA but also cAMP , calmodulin  and c-MYC mRNA induction .
We have previously demonstrated that application of rTMS to the brain inhibits dysgeusia and dysosmia  consistent with its effect on neuroplasticity [5,66] as previously shown in several studies involving these patients [2,3,5]. The concentration of calcium is a major regulator of glutamic acid decarboxylase (GAD) activity  and GABAB receptors show a close homology to the calcium sensory receptor which responds to changes in extracellular calcium . Calcium channels serve as part of the GABA release system from striatal brain slices . Thus, the increases we have observed in plasma calcium after rTMS may be a manifestation of a complex system in which calcium not only plays a significant metabolic role but also a role in neuroplasticity such as we have observed with the inhibition of dysgeusia and dysosmia.
rTMS inhibits dysosmia and dysgeusia in patients with these symptoms and increases their plasma calcium both in vivo and in vitro. These changes may relate to changes in calcium metabolism and levels of GABA and other neurotransmitters that are affected by rTMS and influence neuroplasticity.
- Henkin RI, Levy LM, Lin CS (2000) Taste and smell phantoms revealed by brain functional MRI (fMRI). J Comput Assist Tomogr. 24: 106-123.
- Levy LM, Henkin RI (2004) Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy. J Comput Assist Tomogr 28: 721-727.
- Henkin RI, Potolicchio SJ, Levy LM (2013) Olfactory hallucinations without clinical motor activity: a comparison of unirhinal withbirhinalphantosmia. Brain Sci 3(4): 1483-1553.
- Henkin RI, Potolicchio SJ, Levy LM (2011) Improvement in smell and taste dysfunction after repetitive transcranial magnetic stimulation. Am J Otolaryngol32: 38-46.
- Henkin RI, Potolicchio SJ, Levy LM (2000) Rapid changes in taste and smell function following transcranial magnetic stimulation (TCMS) in humans: relationships to CNS plasticity. FASEB J 16: A875.
- Zangen A, Hyodo K (2002) Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens. Neuroreport 13: 2401-2405.
- Ziemann U (2004) TMS and drugs. ClinNeurophysiol 115: 1717-1729.
- Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y (2004) Effects of acute repetitive transcranial magnetic stimulation on dopamine release in the rat dorsalateral striatum. J NeurolSci 217: 73-81
- Funamizu H, Ogiue-Ikeda M, Mukai H, Kawato S, Ueno S (2005) Acute repetitive transcranial magnetic stimulation reactive-dopaminergic system in lesion rats. NeurosciLett 383: 77-81
- Strafella AP, Paus T, Barrett J, Dagher A (2001) Repetitive transcranial magnetic stimulation of the prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 21: RC157.
- Ziemann U, Tergau F, Bruns D, Baudewig J, Paulus W (1997) Changes in human motor cortex excitability induced by dopaminergic and anti-dopaminergic drugs. ElectroencephalogrClinNeurophysiol/Electromyogr Motor Control 105: 430-437.
- Shaul U, Ben-Shachar D, Karry R, Klein E (2003) Modulation of frequency and duration of repetitive magnetic stimulation affects catecholamine levels and tyrosine hydroxylase activity in human neuroblastoma cells: implication for the antidepressant effect of rTMS. Int J Neuropsychopharmacol 6: 233-241.
- Fleischmann A, Sternheim A, Etgen AM, Li C, Grisaru N, et al. (1996) Transcranial magnetic stimulation downregulates beta-andrenoreceptors in rat cortex. J Neural Transm 103: 1361-1366.
- Keck ME, Sillaber I, Ebner K, Welt T, Toschi N, et al. (2000) Acute transcranial magnetic stimulation of frontal brain regions selectively modulates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur J Neurosci 12: 3713-3720.
- Oliveri M, Calvo G (2003) Increased visual cortical excitability in ecstasy users: a transcranial magnetic stimulation study. J NeurolNeurosurg Psychiatry 2003 74:1136-1138.
- Juckel G, Mendlin A, Jacobs BL (1999) Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin output: implications for electroconvulsive therapy and transcranial magnetic stimulation in depression. Neuropsychopharmacology 21:391-398.
- Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y (2003) Effects of acute repetitive transcranial magnetic stimulation on extracellular serotonin concentration in the rat prefrontal cortex. J PharmacolSci 93; 451-457.
- Capaday C, Richardson MP, Rothwell JC, Brooks DJ (2000) Long-term changes of GABAergic function in the sensorimotor cortex of amputees: a combined magnetic stimulation and 11C-flumazenil PET study. Exp Brain Res 133: 552-556.
- De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, et al. (2005) Transcranial magnetic stimulation for tinnitus: influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression. OtolNeurotol 26: 616-619.
- Eichhammer P, Langguth B, Zowe M, Kleinjung T, Jacob P, et al. (2004) GABA-B-associated neuropsychiatric disorders. PsychiatrPrax 31(suppl 1): S44-S46.
- Gur E, Lerer B, van de Kar LD, Newman ME (2004) Chronic rTMS induces subsensitivity of post-synaptic 5-HT1A receptors in rat hypothalamus. Int J Neuropsychopharmacol 7: 335-340.
- Pascual-Leone A, Tormos JM, Keenan J, Tarazona F, Cañete C, et al. (1998) Study and modulation of human cortical excitability with transcranial magnetic stimulation. ClinNeurophysiol 15: 333-343.
- Hallett M (2000) Transcranial magnetic stimulation and the human brain. Nature 406: 147-150.
- Fuhr P, Agostino R, Hallett M (1991) Spinal motor neuron excitability during the silent period after cortical stimulation. ElectroencephClinNeurophysiol 81: 257-262.
- Ziemann U, Lönnecker S, Steinhoff BJ, Paulus W (1996) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol 40: 367-378.
- Nakamura H, Kitagawa H, Kawaguchi Y, Tsuji H (1997) Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. J Physiol 498: 817-823.
- Merabet LB, Theoret H, Pascual-Leone A (2003) Transcranial magnetic stimulation as an investigative tool in the study of visual function. Optom Vis Sci 80: 356-368.
- Jahanshahi M, Rothwell J (2000) Transcranial magnetic stimulation of cognition: an emerging field. Exp Brain Res 131: 1-9.
- Robertson EM, Theoret H, Pascual-Leone A (2003) Studies in cognition: the problems solved and created by transcranial magnetic stimulation. J CognNeurosci 15: 945-960.
- Evers S, Böckermann I, Nyhuis PW (2001) The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. Neuroreport 12: 2915-2918.
- Kobayashi M, Pascual-Leone A (2003) Transcranial magnetic stimulation in neurology. Lancet Neurol 2: 145-156.
- Boroojerdi B, Phipps M, Kopylev L, Wharton CM, Cohen LG, et al. (2001) Enhancing analogic reasoning with rTCMS over the left prefrontal cortex. Neurology. 56: 526-528.
- Khedr EM, Ahmed MA., Fathy N, Rothwell JC (2005) Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology 65: 466-468.
- Turton A, Wroe S, Trepte N, Fraser C, Lemon RN (1996) Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke. ElectroencephalogrClinNeurophysiol 101: 316-328.
- Mally J, Stone TW (1999) Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation. J NeurolSci 162: 179-184.
- Siebner HR, Mentschel C, Auer C, Conrad B (1999) Repetitive transcranial magnetic stimulation has a beneficial effect on bradykinesia in Parkinson’s disease. Neuroreport 10: 589-594.
- Hoffman RE, Boutros NN, Hu S, Berman RM, Krystal JH, et al. (2000) Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet 355: 1073-1075.
- d’Alfonso AA, Aleman A, Kessels RP, Schouten EA, Postma A, et al. (2000) Transcranial magnetic stimulation (TCMS) of left auditory cortex in patients with schizophrenia: effects on hallucinations and neurocognition. J NeuropsychiatrClinNeurosci 14: 77-79.
- Fitzgerald PB, Benitez J, Daskalakis JZ, Brown TL, Marston NA, et al. (2005) A double-blind-sham-controlled trial of repetitive transcranial magnetic stimulation with treatment of refractory auditory hallucinations. J ClinPsychopharmacol 25: 358-362.
- Plewnia C, Bartels M, Gerloff C (2003) Transient suppression of tinnitus by transcranial magnetic stimulation. Ann Neurol53: 263-266.
- Moharram R, Potolicchio SJ, Velicu I, Martin BM, Henkin RI (2004) Growth factor regulation in human olfactory system function: the role of transcranial magnetic stimulation. FASEB J 18: A201.
- Henkin RI, Potolicchio SJ, Levy LM, Moharram R, Velicu I, et al. (2010) Carbonic anhydrase (CA) I, II and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation. Am J Med Sci 339: 249-257.
- Henkin RI, Levy LM, Fordyce A (2013) Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol 34: 477-489.
- Henkin RI (1992) Phantageusia. In: Taylor RB, editor. Difficult Diagnosis II. Philadelphia: W.B Saunders: 348-356.
- Schechter PJ, Henkin RI (1974) Abnormalities of taste and smell after head trauma. J. Neurol. Neurosurg. Psychiatry 37: 802-810.
- Henkin RI, Larson AL, Powell RD (1975) Hypogeusia, dysgeusia, hyposmia and dysosmia following influenza-like infection. Ann OtolRhinLaryngol 84: 672-682.
- Henkin RI (1993) Evaluation and treatment of human olfactory dysfunction. In: English GM, editor. Otolaryngology. Vol. 2. Philadelphia Lippincott: 1-86.
- Henkin RI (1994) Drug induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction. Drug Saf 11: 318-377.
- Meret S, Henkin RI (1971) Simultaneous direct estimation by atomic absorption spectrophotometry of copper and zinc in serum, urine, and cerebrospinal fluid. ClinChem 17: 369-373.
- Liburdy RP (1995) Cellular studies and interaction mechanisms of extremely low frequency fields. Radio Sci 30: 179-203.
- Pessina GP, Aldinucci C, Palmi M, Sgaragli G, Benocci A, et al. (2001) Pulsed electromagnetic fields affect the intracellular calcium concentrations in human astrocytoma cells. Bioelectromagnetics 22: 503-510.
- Fitzsimmons RJ, Ryaby JT, Magee FP, Baylink DJ (1994) Combined magnetic fields increased net calcium flux in bone cells. Calcif Tissue Int 55: 376-380.
- Yost MG, Liburdy RP (1992) Time-varying and static magnetic fields act in combination to alter calcium signal transduction in the lymphocyte. FEBS Lett 296: 117-122.
- Lindström E, Lindström P, Berglund A, Lundgren E, Mild KH (1995) Intracellular calcium oscillations in a T-cell line after exposure to extremely-low-frequency magnetic fields with variable frequencies and flux densities. Bioelectromagnetics 16: 41-47.
- Cho MR, Thatte HS, Silvia MT, Golan DE (1999) Transmembrane calcium influx induced by ac electric fields. FASEB J 13: 677-683.
- Teodori L, Göhde W, Valente MG, Tagliaferri F, Coletti D, et al. (2002) Static magnetic fields affect calcium fluxes and inhibit sress-induced apoptosis in human glioblastoma cells. Cytometry 49: 143-149.
- Farndale RW, Maroudas A, Marsland TP (1987) Effects of low-amplitude pulsed magnetic fields on cellular ion transport. Bioelectromagnetics 8: 119-134.
- Persinger MA, Carrey NC, Lafrenière GF, Mazzuchin A (1978) Thirty-eight blood, tissue and consumptive measures from rats exposed perinatally and as adults to 0.5 Hz magnetic fields. Int J Biometeor 22: 213-226.
- Walleczek J (1992) Electromagnetic field effects on cells of the immune system: the role of calcium signaling. FASEB J 6: 3177-3185.
- DeLorenzo RJ, Sun DA, Deshpande LS (2005) Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy. PharmacolTher 105: 229-266.
- Mills LR (1991) Neuron-specific and state-specific differences in calcium regulation. Ann NY AcadSci 639: 312-324.
- Ghosh A, Greenberg ME (1995) Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science. 268: 239-247.
- Pittenger D, Duman RS (2008) Stress, depression and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology. 33: 88-109.
- Hendee SP, Faour FA, Christensen DA, Patrick B, Durney CH, et al. (1996) The effects of weak extremely low frequency magnetic fields on calcium/calmodulin interactions. Biophys J 70: 2915-2923.
- Liburdy RP, Callahan DE, Harland J, Dunham E, Sloma TR, et al. (1993) Experimental evidence for 60 Hz magnetic fields operating through the signal transduction cascade: effects on calcium influx and c-MYC mRNA induction 334: 301-308.
- Gersner R, Kravetz E, Feil J, Pell G, Zangen A (2011) Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: differential outcomes in anesthetized and awake animals. J Neurosci 31: 7521-7526.
- Erecinska M, Nelson D, Daikhin Y, Yudkoff M (1996) Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium and ketone bodies. J Neurochem 67: 2325-2334.
- Wise A, Green A, Main MJ, Wilson R, Fraser N, et al. (1999) Calcium sensing properties of the GABA(B) receptor. Neuropharmacology 38: 1647-1656.
- Bernath S, Zigmond MJ (1990) Calcium-independent GABA release from striatal slices: the role of calcium channels. Neuroscience 36: 677-682.
Citation: Stateman WA, Knöppel A, Potolicchio SJ, Henkin RI (2014) Repetitive Transcranial Magnetic Stimulation (Rtms) increases Plasma Calcium both in-vivo and in-vitro. J Clin Exp Pathol 4:187. Doi: 10.4172/2161-0681.1000187
Copyright: © 2014 Stateman WA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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