Effect of nifedipine on the ion channels formed by alpha(1) subunits of the cardiac and vascular muscle L-type Ca channels
(1999) Neurophysiology — Vol. 31, n° 6, p. 361-364 (1999)
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- We investigated the voltage dependence of nifedipine sensitivity of the ion channels formed by at subunits of the cardiac and smooth muscles (CM and SM, respectively) L-type Ca2+ channels stably expressed in Chinese hamster ovary (CHO) cells. Equilibrium inhibition of the alpha(1) subunits, directing Ba2+ current (I-alpha 1), by different concentrations of nifedipine was measured at the holding potentials (V-h) of -100 mV and -50 mV. At V-h = -100 mV, the SM alpha(1) subunit was found to be 6-fold more sensitive for nifedipine than the subunit (K-100 = 8.3 and 50.4 nM, respectively). Depolarization to -50 mV resulted in about sevenfold increase in the nifedipine potency for both subunits (K-50 = 1.25 and 6.95 nM, respectively). The voltage dependence of steady-state inactivation could be fitted by a sum of two Boltzmann's equations with slope factors of about 12 and 5 mV. The midpoints of both components in the CM at subunit (-75.6 and -42.8 mV) were more negative than those in the SM subunit (63.7 and -37.7 mV). The relative contribution of the less sloped component in the control was rather low, being less pronounced in the CM (0.15) than in the SM (0.34) subunits. Nifedipine shifted the midpoints of inactivation curves to more negative potentials. The shift was more pronounced for the SM ar subunit (-24.8 mV compared with -11.8 mV for the CM subunit in the presence of 10 nM nifedipine). Nifedipine differentially affected the two Boltzmann components of inactivation curves, more effectively inhibiting the steeper component. In the presence of 10 nM nifedipine, this component completely disappeared in the SM subunit. while its relative contribution in the CM subunit decreased from 0.85 to 0. 57, resulting in an apparent decrease in the steepness. These results are inconsistent with the receptor modulated hypothesis and suggest the existence of two mechanisms of inactivation characterized by different voltage dependence.
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Bouryi, V. (1999). Effect of nifedipine on the ion channels formed by alpha(1) subunits of the cardiac and vascular muscle L-type Ca channels. Neurophysiology, 31(6), 361-364. https://doi.org/10.1007/BF02515136 (Original work published 1999)