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 microM) 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.


CONCLUSIONS
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.
Ferrier
Gregory R
GR
Department of Pharmacology, Sir Charles Tupper Medical Bldg., Dalhousie University, Nova Scotia, Halifax, Canada. gregory.ferrier@dal.ca
Redondo
Isabel
I
Zhu
Jiequan
J
Murphy
Mary G
MG
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D003864:Depression, Chemical; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D020746:Calcium Channels, L-Type; D002104:Cadmium; D004281:Docosahexaenoic Acids