Inhibition of voltage-dependent Ca2+ channels of porcine tracheal smooth muscle by the novel Ca2+ channel antagonist RWJ-22108.
1. We compared electrophysiological effects of the bronchoselective Ca2+ channel antagonist RWJ-22108 on voltage-dependent Ca2+ channels (VDCs) of porcine tracheal smooth muscle cells to the effects of nicardipine and verapamil. 2. Each of the three Ca2+ channel antagonists tested inhibited inward Ca2+ currents (ICa) measured by whole-cell patch clamp techniques. Inhibition was dose-dependent with approximately 50% inhibition of peak ICa at +20 mV obtained with 3 x 10(-6) M RWJ-22108, 3 x 10(-7) M nicardipine, or 10(-5) M verapamil. 3. Both RWJ-22108 (3 x 10(-6) M) and nicardipine (3 x 10(-7) M) shifted the voltage dependence of steady-state inactivation to more negative potentials; however, the change in the potential of half-maximal inactivation induced by RWJ-22108 (-18 mV) was significantly greater than that induced by nicardipine (-12 mV). Verapamil did not alter the voltage dependence of inactivation. 4. We conclude that inhibition of VDCs by RWJ-22108 is qualitatively similar to that by nicardipine but with a greater stabilizing effect on the inactivated channel state.
Yamakage
M
M
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Hirshman
C A
CA
Namiki
A
A
Croxton
T L
TL
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011725:Pyridines; C080337:RWJ 22108; D014700:Verapamil; D009529:Nicardipine