Sodium permeability of frog skeletal muscle in absence and presence of veratridine.
The effect of veratridine on the Na permeability of frog sartorius muscle was studied by means of ion flux measurements using radiolabeled sodium. Veratridine increases Na influx in a dose-dependent manner (apparent Kd = 160 +/- 7 microM when Vm congruent to -40 mV). The increase can be completely inhibited by tetrodotoxin (TTX) (apparent Ki = 8 +/- 2 nM), indicating that all veratridine-induced Na influx occurs via sodium channels. The time constant for the rate of onset of veratridine action is 1 h. Raising external pH one unit to 8.3 causes the rate of action of veratridine and the final level of Na influx to increase. The apparent Kd for veratridine depends on membrane voltage. Values obtained in 2.5 and 5 mM K Ringer (Vm congruent to -95 and -80 mV) were 579 +/- 279 and 35 +/- 8 microM, respectively. Veratridine-induced Na influx obeys the Goldman constant field flux equation and when veratridine concentration is 1 mM, sodium permeability is 1.5 X 10(-7) cm/s. This is much less than the maximum PNa (1.6 X 10(-3) cm/s) obtained from voltage-clamp measurements of peak Na conductance. Mg (52 mM) inhibits veratridine-induced influx by about half. Aspects of resting Na influx in the absence of veratridine (but in the presence of ouabain) were also characterized. Steady-state Na influx is unaffected by tetrodotoxin over the voltage range -90-0 mV, suggesting that no sodium channels are open in the resting state. Na influx is also insensitive to curare. It is linearly dependent on external sodium and larger at more negative membrane potentials.
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D009132:Muscles / Q000378:metabolism*; D011894:Rana pipiens; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D007473:Ion Channels; D013779:Tetrodotoxin; D014701:Veratridine; D012964:Sodium; D014702:Veratrine; D008274:Magnesium