Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells.
Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.
Kramer
R H
RH
Center for Neurobiology and Behavior, Columbia University of Physicians and Surgeons, New York, NY 10032.
Mokkapatti
R
R
Levitan
E S
ES
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats
D015220:Calcium Channels; D002110:Caffeine; D011188:Potassium; D002118:Calcium