OMEGA-3 POLYUNSATURATED FATTY-ACID MODULATES DIHYDROPYRIDINE EFFECTS ON L-TYPE CA2+ CHANNELS, CYTOSOLIC CA2+, AND CONTRACTION IN ADULT-RAT CARDIAC MYOCYTES

The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (I-Ca), cytosolic Ca2+ (Ca-i), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca2+-channel blocker nitrendipine (10 nM) reduced peak I-Ca (measured by whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+ transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the twitch amplitude (measured via photodiode array) during steady-state electrical stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM) significantly increased I-Ca, the amplitude of the Ca-i transient, and contraction. When cells were exposed to DHA (5 mu M) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 mu M did not block the inhibitory effects of nitrendipine nor did it prevent the potentiating effects of BAY K 8644. DHA modulation of DHP action could be reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml. Neither DHA nor arachidonic acid alone (5 mu M) had any apparent effect on the parameters measured. DHA (5 mu M) had no influence over beta-adrenergic receptor stimulation (isoproterenol, 0.01-1 mu M)-induced increases in I-Ca, Ca-i, or contraction. The findings that DHA inhibits the effect of DHP agonists and antagonists on Ca2+-channel current but has no effect alone or on beta-adrenergic-induced increases in I-Ca suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with I-Ca modulation.