title: Resting potential-dependent regulation of the voltage sensitivity of sodium channel gating in rat skeletal muscle in vivo.
abstract: Normal muscle has a resting potential of -85 mV, but in a number of situations there is depolarization of the resting potential that alters excitability. To better understand the effect of resting potential on muscle excitability we attempted to accurately simulate excitability at both normal and depolarized resting potentials. To accurately simulate excitability we found that it was necessary to include a resting potential-dependent shift in the voltage dependence of sodium channel activation and fast inactivation. We recorded sodium currents from muscle fibers in vivo and found that prolonged changes in holding potential cause shifts in the voltage dependence of both activation and fast inactivation of sodium currents. We also found that altering the amplitude of the prepulse or test pulse produced differences in the voltage dependence of activation and inactivation respectively. Since only the Nav1.4 sodium channel isoform is present in significant quantity in adult skeletal muscle, this suggests that either there are multiple states of Nav1.4 that differ in their voltage dependence of gating or there is a distribution in the voltage dependence of gating of Nav1.4. Taken together, our data suggest that changes in resting potential toward more positive potentials favor states of Nav1.4 with depolarized voltage dependence of gating and thus shift voltage dependence of the sodium current. We propose that resting potential-induced shifts in the voltage dependence of sodium channel gating are essential to properly regulate muscle excitability in vivo.
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Dayton, OH 45435, USA.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Filatov
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pinter
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rich
mesh_terms: D000200:Action Potentials; D000818:Animals; D002463:Cell Membrane Permeability; D004558:Electric Stimulation; D005260:Female; D008564:Membrane Potentials; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009124:Muscle Proteins; C466180:Scn4a protein, rat; D015222:Sodium Channels; D012964:Sodium; D011188:Potassium