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⁺∼Ni²⁺∼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. Dedicated by Catherine Van Renterghem to her father, Jacques Van Renterghem