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

GR Ferrier, I Redondo, J Zhu… - Cardiovascular …, 2002 - academic.oup.com
GR Ferrier, I Redondo, J Zhu, MG Murphy
Cardiovascular research, 2002academic.oup.com
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 …
Abstract
Beneficial effects of n−3 polyunsaturated fatty acids in Ca2+ overload have been attributed to blockade of L-type Ca2+ current (ICa-L). However, cardiac contractions may be maintained despite block of ICa-L. 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 μM) 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 ICa-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 ICa-L, may explain the ability of n−3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function.
Oxford University Press