Electrophysiological characterization of sodium channel types in the HCN-1A human cortical cell line.
Electrically evoked sodium currents were recorded under whole-cell patch clamp from undifferentiated HCN-1A cells. Peak sodium currents had a half-maximal activation, Vm0.5, of -22.6 +/- 1.0 mV with a voltage dependence, km, of 7.28 +/- 0.39 mV-1. Steady-state inactivation indicated the presence of two types of sodium channel. One type inactivated with Vh0.5 = -93.8 +/- 1.2 mV and kh = -6.8 +/- 0.4 mV-1. The second type of sodium channel inactivated with Vh0.5 = -44.6 +/- 1.5 mV and kh = -7.3 +/- 0.4 mV-1. The occurrence of each channel type varied from cell to cell and ranged from 0 to 100% of the total sodium current. No variation in the rate of inactivation was seen when the holding potential was adjusted to eliminate the more negative of the two inactivation components. Application of tetrodotoxin (TTX) or saxitoxin (STX) revealed channel types with two different affinities for each toxin. TTX blocked peak sodium conductance with apparent IC50s of 22 nM and 5.3 microM. STX was more potent, with apparent IC50s of 1.6 nM and 1.2 microM. There was no statistical correlation between toxin sensitivity and steady-state inactivation voltage, suggesting that these properties varied independently among sodium channel types.
Sheridan
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Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D012530:Saxitoxin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin