ω3 Polyunsaturated fatty acid modulates dihydropyridine effects on L- type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes

S. Pepe, K. Bogdanov, H. Hallaq, H. Spurgeon, A. Leaf, E. Lakatta

Research output: Contribution to journalArticlepeer-review

Abstract

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 μM) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 μM 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 μM) had any apparent effect on the parameters measured. DHA (5 μM) had no influence over β-adrenergic receptor stimulation (isoproterenol, 0.01-1 μM)-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 β-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.

Original languageEnglish (US)
Pages (from-to)8832-8836
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • indo-1 fluorescence
  • patch-clamp recording

ASJC Scopus subject areas

  • General

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