Journal of Neurophysiology, Vol 69, Issue 5 1596-1606, Copyright © 1993 by APS

ARTICLES

Calcium currents in acutely isolated human neocortical neurons

R. J. Sayer, A. M. Brown, P. C. Schwindt and W. E. Crill
Department of Physiology and Biophysics, University of Washington, Seattle 98195.

1. Ca2+ currents were investigated in neurons acutely isolated from adult human temporal neocortex. The aim was to compare the basic characteristics of the currents with those previously described in animals and to examine the effects of dihydropyridine Ca2+ antagonists and antiepileptic drugs. The tissue, obtained from patients undergoing temporal lobe surgery for medically intractable epilepsy, was sliced, incubated in papain, and triturated. 2. Most of the isolated neurons (34 of 36) were judged to be pyramidal cells by their morphology. Whole-cell voltage-clamp recordings revealed two components of Ca2+ current: 1) a low-threshold (T-type) current that was transient, small in amplitude, and required hyperpolarization more negative than -70 mV for removal of inactivation and 2) a high-threshold current that was slowly inactivating and was available for activation from more positive potentials. The characteristics of the Ca2+ currents were very similar to those in the neocortical neurons of young rats, although the low-threshold current was less prominent in the human cells. 3. Subcomponents of the high-threshold current were identified by pharmacology. About 20% of the peak current was blocked by omega-conotoxin GVIA (presumed N current) and 40-50% of the peak current was blocked by micromolar concentrations of the dihydropyridine Ca2+ antagonists nifedipine and nimodipine (presumed L current). In two neurons tested with a range of nimodipine concentrations, the threshold for suppression of the high-threshold current was approximately 10 nM. 4. The antiepileptic agents ethosuximide, carbamazepine, and valproate did not affect the Ca2+ currents at therapeutically relevant concentrations. Phenytoin marginally reduced the low- and high-threshold Ca2+ currents at 8 microM (a concentration corresponding to the upper therapeutic range). The results do not support the hypothesis that inhibition of Ca2+ currents in neocortical pyramidal neurons is a major action of these drugs.

This article has been cited by other articles:

				M. Manuel, C. Meunier, M. Donnet, and D. Zytnicki Resonant or Not, Two Amplification Modes of Proprioceptive Inputs by Persistent Inward Currents in Spinal Motoneurons J. Neurosci., November 21, 2007; 27(47): 12977 - 12988. [Abstract] [Full Text] [PDF]

				H. Khosravani and G. W. Zamponi Voltage-gated calcium channels and idiopathic generalized epilepsies. Physiol Rev, July 1, 2006; 86(3): 941 - 966. [Abstract] [Full Text] [PDF]

				N. Keren, N. Peled, and A. Korngreen Constraining Compartmental Models Using Multiple Voltage Recordings and Genetic Algorithms J Neurophysiol, December 1, 2005; 94(6): 3730 - 3742. [Abstract] [Full Text] [PDF]

				H. Zhou, S.-A. Kim, E. A. Kirk, A. L. Tippens, H. Sun, F. Haeseleer, and A. Lee Ca2+-Binding Protein-1 Facilitates and Forms a Postsynaptic Complex with Cav1.2 (L-Type) Ca2+ Channels J. Neurosci., May 12, 2004; 24(19): 4698 - 4708. [Abstract] [Full Text] [PDF]

				E. Perez-Reyes Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels Physiol Rev, January 1, 2003; 83(1): 117 - 161. [Abstract] [Full Text] [PDF]

				J. C. Gomora, A. N. Daud, M. Weiergraber, and E. Perez-Reyes Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs Mol. Pharmacol., November 1, 2001; 60(5): 1121 - 1132. [Abstract] [Full Text] [PDF]

				A. Stewart and R. C. Foehring Calcium Currents in Retrogradely Labeled Pyramidal Cells From Rat Sensorimotor Cortex J Neurophysiol, April 1, 2000; 83(4): 2349 - 2354. [Abstract] [Full Text] [PDF]

				H. Beck, R. Steffens, U. Heinemann, and C. E. Elger Ca2+-Dependent Inactivation of High-Threshold Ca2+ Currents in Hippocampal Granule Cells of Patients With Chronic Temporal Lobe Epilepsy J Neurophysiol, August 1, 1999; 82(2): 946 - 954. [Abstract] [Full Text] [PDF]

				A. E. Stewart, Z. Yan, D. J. Surmeier, and R. C. Foehring Muscarine Modulates Ca2+ Channel Currents in Rat Sensorimotor Pyramidal Cells Via Two Distinct Pathways J Neurophysiol, January 1, 1999; 81(1): 72 - 84. [Abstract] [Full Text] [PDF]

				N. Leresche, H. R. Parri, G. Erdemli, A. Guyon, J. P. Turner, S. R. Williams, E. Asprodini, and V. Crunelli On the Action of the Anti-Absence Drug Ethosuximide in the Rat and Cat Thalamus J. Neurosci., July 1, 1998; 18(13): 4842 - 4853. [Abstract] [Full Text] [PDF]

				H. Beck, R. Steffens, U. Heinemann, and C. E. Elger Properties of Voltage-Activated Ca2+ Currents in Acutely Isolated Human Hippocampal Granule Cells J Neurophysiol, March 1, 1997; 77(3): 1526 - 1537. [Abstract] [Full Text] [PDF]

				B. Yu and P. Shinnick-Gallagher Dihydropyridine- and Neurotoxin-Sensitive and -Insensitive Calcium Currents in Acutely Dissociated Neurons of the Rat Central Amygdala J Neurophysiol, February 1, 1997; 77(2): 690 - 701. [Abstract] [Full Text] [PDF]