TUBOCURARINE BLOCKS A CALCIUM-DEPENDENT POTASSIUM CURRENT IN RAT TUMORAL PITUITARY-CELLS

We investigated the effects of potassium channel inhibitors on electri cal activity, membrane ionic currents, intracellular calcium concentra tion ([Ca2+](i)) and hormone release in GH(3/)B6 cells (a line of pitu itary origin). Patch-clamp recordings show a two-component after hyper polarization (AHP) following each action potential (current-clamp) or a two-component tail current (voltage-clamp). Both components can be b locked by inhibiting Ca2+ influx. Application of D-tubocurarine (dTc) (20-500 mu M) reversibly suppressed the slowly decaying Ca2+-activated K+ tail current (I AHPs) in a concentration-dependent manner. On the other hand, low doses of tetraethylammonium ions (TEA(+)) only blocked the rapidly decaying voltage- and Ca2+-activated K+ tail current (I A HPf). Therefore, GH(3)/B6 cells exhibit at least two guile distinct Ca 2+-dependent K+ currents, which differ in size, voltage- and Ca2+-sens itivity, kinetics and pharmacology. These two currents also play quire separate roles in shaping the action potential. d-tubocurarine increa sed spontaneous Ca2+ action potential firing, whereas TEA increased ac tion potential duration. Thus, both agents stimulated Ca2+ entry. I AH Ps is activated by a transient increase in [Ca2+](i) such as a thyrotr ophin releasing hormone-induced Ca2+ mobilization. All the K+ channel inhibitors we tested: TEA, apamin, dTC and charybdotoxin, stimulated p rolactin and growth hormone release in GH(3)/BS cells. Our results sho w that I AHPs is a good sensor for subplasmalemmal Ca2+ and that dTc i s a good pharmacological tool for studying this current. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.