Nitrendipine inhibition of calcium current in rat vascular muscle cells.
The effect of nitrendipine on spontaneous contraction frequency and Ca2+ currents was studied in spontaneously active rat azygos venous cells in primary culture. Nitrendipine reduced the frequency of contraction in a concentration-dependent manner, with 50% inhibition (IC50) at approximately 10(-7) M. In similar cells using the whole-cell voltage-clamp technique, nitrendipine (10(-7) M) reduced the peak magnitude of the longer lasting, high-threshold (L) Ca2+ channel current by 52 +/- 6%, while the transient, low-threshold (T) Ca2+ channel current was unaffected. As estimated from the current-voltage inactivation relationship, the dissociation constant (Kd) for nitrendipine binding to the resting state of Ca2+ channels was 108 nM for the L channel and greater than 2 microM for the T channel. This high-affinity binding of the dihydropyridine to the resting state of the L channel in vascular muscle contrasts with the lower-affinity binding reported in cardiac muscle. Thus, nitrendipine may inhibit spontaneous activity in vascular muscle cells at least partly by blocking Ca2+ current through L channels.
Hermsmeyer
K
K
Chiles Research Laboratory, Providence Medical Center, Portland, OR 97213.
Sturek
M
M
Rusch
N J
NJ
D000818:Animals; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects*; D004563:Electrochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D014680:Veins / Q000166:cytology / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009568:Nitrendipine