title: Modulation of electrical activity and of intracellular calcium oscillations of smooth muscle cells by calcium antagonists, agonists, and vasopressin.
abstract: The A7r5 smooth muscle cell line, which originally was derived from fetal rat aorta, shows spontaneous calcium oscillations associated with electrical activity (frequency of 0.2-0.5 Hz). Organic calcium antagonists such as isradipine (10(-8) M) stopped the calcium oscillations whereas calcium agonists (e.g., Bay K 8644, 10(-8) M) increased the frequency and amplitude of calcium oscillations without changing the shape of the electrical spikes. The enantiomers of the dihydropyridine SDZ 202-791 known to have opposite activity with respect to L-type Ca2+ channels antagonized each other when tested for their effects on the calcium oscillations. The modulation of the activity of these cells by inorganic ions that affect Ca2+ and K+ channels was also investigated. The addition of barium chloride (10(-4) M) to the bathing solution increased the spiking rate whereas cadmium chloride (10(-6) M) abolished the spikes. The vasoconstrictor peptide vasopressin first induced a hyperpolarization associated with the cessation of spiking activity followed by a slow depolarization. The intracellular Ca2+ concentration ([Ca2+]i), measured with the calcium indicator fura-2, was increased transiently to a level about 10-fold above basal and then gained a new steady state at about twice the basal level. Vasopressin stimulated Ca2+ release from intracellular stores (via InsP3), resulting in membrane hyperpolarization through activation of Ca(2+)-activated K+ channels. The late and long-lasting [Ca2+]i elevation was due to Ca2+ influx through dihydropyridine-insensitive channels.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Sandoz Pharma Ltd., Basel, Switzerland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Knot
authors.forename: M M
authors.initials: MM
authors.lastname: de Ree
authors.forename: B H
authors.initials: BH
authors.lastname: Gähwiler
authors.forename: U T
authors.initials: UT
authors.lastname: Rüegg
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000032:analysis*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D017275:Isradipine; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000187:drug effects; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014667:Vasopressins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C045796:SAN 202791; D002118:Calcium; D017275:Isradipine