Pharmacological modulation of calcium and potassium channels in isolated vascular smooth muscle cells.
Calcium antagonists relax vascular smooth muscle cells (VSM) by decreasing Ca-influx and intracellular Ca-load. In isolated VSM, Ca-influx was measured as Ca-current by the voltage clamp technique applied to a patch of membrane (single-channel current) or to the whole cell (whole-cell current ICa). Gallopamil exerted Ca-antagonism mostly by reducing channel availability, i.e. the probability that the Ca-channel opens upon depolarization. Whole-cell-Ca-currents revealed prominent frequency dependence, i.e. reduction of ICa increased with the number of depolarizations. In addition, the gallopamil effect was voltage-dependent such that depolarized myocytes were more sensitive than hyperpolarized cells. The dihydropyridine nitrendipine abbreviated the life time which the Ca-channel stood in the open state and it hindered the channel to re-open again. Reduction of availability was found only after a prolonged application. In whole cell ICa, nitrendipine accelerated the inactivation time course. The Ca-antagonistic effect was voltage-dependent but not frequency-dependent. Potassium agonists are supposed to activate K-channels thereby hyperpolarizing the membrane, hyperpolarization shuts off the Ca-channels and thereby reduces Ca-influx. The K-agonists cromakalim, (+) niguldipine and diazoxide activated the Ca-dependent maxi K-channel (inside-out patches studied at [Ca2+]c of 50 nmol/l or 500 nmol/l. They increased the open probability mainly by decreasing the long closures between the channel openings. The K-agonists can repolarize the cell once it excited and suppress further excitability.
Klöckner
U
U
Lehrstuhl für angewandte Physiologie der Universität zu Köln, Fed. Rep. of Germany.
Trieschmann
U
U
Isenberg
G
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009568:Nitrendipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D013552:Swine
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels; D005711:Gallopamil; D009568:Nitrendipine