1. Archive
2. Vol.52, No.6

The Mechanism of Increasing Ca²⁺ Responsiveness by α₁-Adrenoceptor Stimulation in Rat Ventricular Myocytes

Abstract: We investigated the mechanism of α₁-adrenoceptor stimulation on the myofibrillar Ca²⁺ responsiveness at steady-state in intact rat ventricular myocytes. We produced tetanus, and an instantaneous plot of [Ca²⁺]_i vs. cell length (Ca–L trajectory) was constructed to estimate the Ca²⁺ responsiveness. An α₁-agonist, phenylephrine, dose-dependently shifted the Ca–L trajectory to the left, corresponding to sensitization of the myofilaments. An α₁-antagonist, prazosin, and inhibition of the Na/H exchange by ethylisopropylamiloride (EIPA) completely reversed the phenylephrine-induced shift. Phenylephrine increased pH_i (ΔpH_i = +0.1), which was reversed by prazosin and EIPA. Chelerythrine, an inhibitor of protein kinase C (PKC), completely blocked the effects of phenylephrine on Ca²⁺ responsiveness and pH_i. When pH_i was increased (ΔpH_i = +0.1) without phenylephrine by changing pH_o, the Ca–L trajectory was shifted to the same extent as that observed with phenylephrine. We conclude that α₁-adrenoceptor stimulation activates Na/H exchange through a PKC-mediated pathway and that an increase in pH_i is mainly responsible for the increase in Ca²⁺ responsiveness.

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