Differential effects of docosahexaenoic acid on contractions and L-type Ca2+ current in adult cardiac myocytes

Beneficial effects of n-3 polyunsaturated fatty acids in Ca2+ overload have been attributed to blockade of L-type Ca2+ current However, cardiac contractions may be maintained despite block of Objective: This study investigates the cellular basis by which docosahexaenoic acid (DHA), a representative n-3 polyunsaturated fatty acid. inhibits ICa-L while preserving contraction. Methods: Experiments were conducted in adult guinea pig ventricular myocytes with Na+ currents blocked. Contractions initiated by the voltage-sensitive release mechanism (VSRM) and calcium-induced calcium release (CICR) triggered by ICa-L, were activated separately with voltage clamp techniques, Results: DHA (10 muM) inhibited ICa-L and CICR contractions but not VSRM contractions, CICR contractions exhibited a bell-shaped voltage-dependence. However. in the presence of DHA, only contractions with a sigmoidal voltage-dependence characteristic of the VSRM remained. These contractions exhibited inactivation properties characteristic of the VSRM. DHA abolished ICa-L elicited by test steps from -40 mV. Block was voltage-dependent, as residual was elicited by steps from -70 mV. Cd2+ inhibited residual current, but not contractions initiated by the same activation steps. Conclusion: Preservation of VSRM contractions during block of may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function. (C) 2002 Elsevier Science B.V. All rights reserved.