Modulation of electrical activity and of intracellular calcium oscillations of smooth muscle cells by calcium antagonists, agonists, and vasopressin.
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)
Knot
H J
HJ
Sandoz Pharma Ltd., Basel, Switzerland.
de Ree
M M
MM
Gähwiler
B H
BH
Rüegg
U T
UT
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*
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