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 (I_Ca-L). However, cardiac contractions may be maintained despite block of I_Ca-L. Objective: This study investigates the cellular basis by which docosahexaenoic acid (DHA), a representative n-3 polyunsaturated fatty acid, inhibits I_Ca-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 I_Ca-L, were activated separately with voltage clamp techniques. Results: DHA (10 μM) inhibited I_Ca-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 I_Ca-L elicited by test steps from -40 mV. Block was voltage-dependent, as residual I_Ca-L 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 I_Ca-L, may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca²⁺ influx while preserving cardiac contractile function.