Potassium depolarization elevates cytosolic free calcium concentration in rat anterior pituitary cells through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels.
Changes in membrane potential may influence Ca2+-dependent functions through changes in cytosolic free calcium concentration [( Ca2+]i). This study characterized pharmacologically those voltage-dependent Ca2+ channels in normal rat anterior pituitary cells that are involved in the elevation of [Ca2+]i upon high potassium-induced membrane depolarization. The [Ca2+]i was monitored directly by means of the intracellularly trapped fluorescent indicator fura-2. The addition of K+ (6-100 mM) increased [Ca2+]i in a concentration-dependent manner. The fluorescent signal reached a peak within seconds and then decayed to form a new elevated plateau. K+ at the highest concentration used (100 mM) raised [Ca2+]i by about 450 nM. The K+-induced increase in [Ca2+]i was absent in a Ca2+-free medium. BAY K 8644, a 1,4-dihydropyridine Ca2+ channel agonist, also caused an increase in [Ca2+]i. The maximum response in [Ca2+]i upon stimulation with BAY K 8644 (100 nM) was about 40 nM. The half-maximally effective concentration of BAY K 8644 (100 nM) was about 20 nM. The response in [Ca2+]i upon BAY K 8644-stimulation was abolished in a Ca2+-free medium. Predepolarization with various K+ concentrations enhanced the effect of BAY K 8644 (1 microM) on [Ca2+]i. Pretreatment with BAY K 8644 (1 microM) enhanced the response in [Ca2+]i induced by K+ (25 mM). The addition of Mg2+ (30 mM) and nifedipine (1 microM) lowered the resting [Ca2+]i by about 40 and 20 nM, respectively. Mg2+, nifedipine, nimodipine, Gö 5438, verapamil, and diltiazem inhibited the K+ (25 mM)-induced increase in [Ca2+]i; the order of potency (and half-maximally inhibitory concentrations) were nimodipine = Gö 5438 = nifedipine (approximately 100 nM) greater than verapamil (900 nM) greater than diltiazem (greater than 10 microM) greater than Mg2+ (6 mM). Omega-Conotoxin (100 nM) did not inhibit the K+ (25 mM)-induced increase in [Ca2+]i. These data demonstrate that, over a wide range, membrane depolarization induced by high potassium concentration is indeed associated with increases in [Ca2+]i in normal rat anterior pituitary cells. This elevation of [Ca2+]i is mainly due to an influx of Ca2+ through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels (L-type).
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008978:Mollusk Venoms / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D020960:omega-Conotoxins
D001572:Benzofurans; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005456:Fluorescent Dyes; D007473:Ion Channels; D008978:Mollusk Venoms; D020960:omega-Conotoxins; C053423:Conus magus toxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D016257:Fura-2