Large depolarizations and Bay K 8644 prolong the open state of L-type Ca2+ channels in guinea-pig detrusor smooth muscle cells.
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Requires human validation before clinical consideration; leaves open relevance to detrusor dysfunction.
In smooth muscle cells enzymatically isolated from guinea-pig urinary bladder, Ca2+ channel currents were recorded by conventional cell-attached patch clamp techniques. In most recordings Bay K 8644 (2 microM) was contained in the patch pipette. 2. Closure of Ca2+ channels observed during the repolarizing steps was significantly slowed by preconditioning with large depolarizations (+80 and 100 mV), with or without Bay K 8644 in the pipette. 3. The sum of the unitary Ca2+ channel current traces obtained after large conditioning depolarizations (in the presence of Bay K 8644) showed a slowly deactivating tail current. 4. By use of this slow deactivating feature, the current-voltage relationship of the unitary Ca2+ channel current was continuously measured with a ramp pulse after large depolarization. The slope conductance ranged from 22 to 30 pS, compatible with that of L-type Ca2+ channels. 5. It is concluded that L-type Ca2+ channels in guinea-pig detrusor cells are open for much longer after large depolarizations consistent with their being two channel open states, and that Bay K 8644 prolongs the lifetime of both open states. The underlying mechanisms are discussed.
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Nakayama et al. (1996) studied this question.
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