Abstract
The smooth muscle α1Cb subunit of the L-type calcium channel was expressed alone (CHOα 1 cell) or together with the skeletal β1 (CHOαβ1 cell) subunit or smooth muscle β3 (CHOα 1 β3 cell) subunit in Chinese hamster ovary (CHO) cells. The interaction of the expressed calcium channels with the non-dihydropyridine calcium channel blocker Ro 40-5967 was studied. Ro 40-5967 decreased isradipine binding by an apparent allosteric interaction and blocked the barium inward currents (I Ba) in a voltage- and use-dependent manner in all cells. The steady-state inactivation curves were shifted to hyperpolarizing potentials in the presence of Ro 40-5967. The rate of channel inactivation was increased in CHOα 1 and CHOα 1 β3 cells. The shift in the steadystate inactivation curve and the increase in channel inactivation were less pronounced in CHOα 1 β1 cells than in the other cell lines. Low concentrations of Ro 40-5967 increased I Ba by up to 198% in 33% of the CHOα 1 β1 cells. In addition, higher concentrations of Ro 40-5967 were required to inhibit I Ba in 60% of the CHOα 1 β3 cells. These results suggest that the β subunits modify the interaction of the non-dihydropyridine Ro 40-5967 with the expressed calcium channel α 1 subunit.
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Dedicated to the late Professor Dr. W. Osterrieder
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Welling, A., Lacinova, L., Donatin, K. et al. Expression of the L-type calcium channel with two different β subunits and its modulation by Ro 40-5967. Pflugers Arch. 429, 400–411 (1995). https://doi.org/10.1007/BF00374156
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DOI: https://doi.org/10.1007/BF00374156