Dihydropyridine inhibition of single calcium channels and contraction in rabbit mesenteric artery depends on voltage.

The Journal of Physiology
M T Nelson, J F Worley

Abstract

1. The effects of membrane potential and the dihydropyridine calcium channel inhibitor, nisoldipine, on single calcium channels in the presence of Bay K 8644 and contraction in the presence and absence of Bay K 8644 were examined in the rabbit mesenteric artery. 2. Membrane depolarization decreased the peak average single calcium channel current that could be elicited by a test pulse to 0 mV. The steady-state inactivation relationship could be described by the Boltzmann equation, [1 + exp[Vm-V0.5)/k)]-1, with a steepness factor, k, of 7.1 mV. Nisoldipine shifted the steady-state inactivation curve to more negative potentials by increasing the fraction of test pulses without openings. 3. The degree of nisoldipine inhibition of average single calcium channel currents increased with membrane depolarization. Depolarization of the holding potential from -100 to -55 mV decreased the concentration of nisoldipine needed for 50% inhibition (Kapp) from 12.1 to 1.9 nM in the presence of 1 microM-Bay K 8644. 4. Membrane depolarization by external potassium (K+) of the intact artery in the presence of nisoldipine decreased contractions evoked by depolarizing test pulses. The relationship between membrane potential and contraction could be e...Continue Reading

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