© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Differential effects of docosahexaenoic acid on contractions and L-type Ca2+ current in adult cardiac myocytes
aDepartment of Pharmacology, Sir Charles Tupper Medical Bldg., Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
bDepartment of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
gregory.ferrier{at}dal.ca
* Corresponding author. Tel.: +1-902-494-2550; fax: +1-902-494-1388
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.
KEYWORDS CICR calcium-induced calcium release; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ICa-L, L-type Ca2+ current; PUFA, polyunsaturated fatty acid(s); SR, sarcoplasmic reticulum; TTX, tetrodotoxin; Vh, half maximum steady-state inactivation voltage; VPC, postconditioning potential; VSRM, voltage-sensitive release mechanism
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