TY - JOUR
T1 - ω3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes
AU - Pepe, Salvatore
AU - Bogdanov, Konstantin
AU - Hallaq, Haifa
AU - Spurgeon, Harold
AU - Leaf, Alexander
AU - Lakatta, Edward
PY - 1994/9/13
Y1 - 1994/9/13
N2 - The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (ICa), cytosolic Ca2+ (Cai), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca2+-channel blocker nitrendipine (10 nM) reduced peak ICa (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 ICa, the amplitude of the Cai 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 ICa, Cai, 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 ICa suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with ICa modulation.
AB - The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (ICa), cytosolic Ca2+ (Cai), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca2+-channel blocker nitrendipine (10 nM) reduced peak ICa (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 ICa, the amplitude of the Cai 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 ICa, Cai, 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 ICa suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with ICa modulation.
KW - Indo-1 fluorescence
KW - Patch-clamp recording
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M3 - Article
C2 - 7522322
AN - SCOPUS:0028670297
SN - 0027-8424
VL - 91
SP - 8832
EP - 8836
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -