Identification of the Ca2+ current activated by vasoconstrictors in vascular smooth muscle cells.
The noncontractile aortic cell line A7r5 was chosen to study the effect of the vasoconstrictor peptide vasopressin on transmembrane Ca2+ movements, using conventional whole-cell patch recording techniques. Conditions in which previously characterised vasoconstrictor-modulated currents were suppressed revealed a tiny inward current component (-18 +/- 2 pA, n = 50, at -61 mV in 110 mM CaCl2). The vasopressin-activated inward current was absent when Ca2+ was absent from the extracellular solution, and the current amplitude increased with [Ca2+] (0.01-110 mM), with an apparent dissociation constant for Ca2+ of 9.7 mM. It was highly selective for Ca2+ over monovalent cations (permeability ratio Ca/Cs greater than 17). It was not voltage gated, except that the current/potential characteristic showed some inwards rectification. Amplitudes of the evoked inward currents had the same order of magnitude in Sr2+ and Ca2+, whereas they were much smaller in Mn2+, suggesting that this pathway is highly permeable to Sr2+ but poorly permeable to Mn2+. Inward currents evoked in Ca2+ were inhibited by other cations with the following order of potency: La3+ > Cd2+ > Co2+ approximately Ni2+ approximately Mn2+. The channel producing this current corresponds most probably to the ionic pathway originally called the receptor-operated calcium channel, which produces a long-lasting, constrictor-induced plateau of increased intracellular free calcium concentration in smooth muscle.
Van Renterghem
C
C
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Lazdunski
M
M
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002412:Cations / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D003470:Culture Media; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D002412:Cations; D003470:Culture Media; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin