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- W2002608369 abstract "The patch clamp technique was used to study the nitrendipine block of calcium channels in single cells isolated from cardiac or vascular muscle. Both cardiac cells and vascular muscle cells were found to contain two distinct types of calcium channels. One of these channels, marked by a relatively high threshold for activation and relatively slow inactivation kinetics, and called the “slow‘’ channel, is sensitive to block by low concentrations of nitrendipine. The other channel has a lower threshold for activation and inactivates relatively quickly; it is called the “fast‘’ channel and is relatively insensitive to block by nitrendipine. Nitrendipine block of the slow type of channels was found to be profoundly modulated by the membrane potential of the cell. When calcium currents were elicited by depolarizations from well polarized membrane potentials of – 80 mV or so, concentrations of 100–700 nM nitrendipine were required for half-block of the currents. In contrast, when the membrane potential was held at depolarized potentials of – 10 mV or so, nitrendipine was much more potent as a blocker, with half-block being achieved by concentrations of ∼0.3 nM. The results can be understood by hypothesizing that nitrendipine binds very tightly to the inactivated state of the calcium channel (which predominates at depolarized potentials) and much more weakly to the normal resting state of the channel (which predominates at negative holding potentials). The Kd estimated for binding to inactivated channels is very similar to the dissociation constants found for high-affinity nitrendipine binding to sites in cardiac and smooth muscle. The results suggest that the high-affinity binding site is the inactivated state of the slow type of calcium channel. The results also show that the potency of nitrendipine block can be dramatically altered by resting membrane potential, which may help explain why nitrendipine is so much more potent in inhibiting contraction of smooth muscle (with typically low resting potentials) than contraction of cardiac muscle (with typically high resting potentials)." @default.
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- W2002608369 date "1987-01-01" @default.
- W2002608369 modified "2023-10-16" @default.
- W2002608369 title "Nitrendipine Block of Calcium Channels in Cardiac and Vascular Muscle" @default.
- W2002608369 doi "https://doi.org/10.1097/00005344-198700094-00004" @default.
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