MODULATION OF VOLTAGE-DEPENDENT CA CHANNEL CURRENT BY ARACHIDONIC-ACID AND OTHER LONG-CHAIN FATTY-ACIDS IN RABBIT INTESTINAL SMOOTH-MUSCLE

The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage-dependent Ca channel current (I(Ca)) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30-mu-M AA caused a gradual depression of I(Ca). The inhibitory effect of AA was not prevented by indomethacin (10-mu-M) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10-mu-M) (an inhibitor of lipoxygenase). 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H7; 25-50-mu-M) or staurosporine (2-mu-M) (inhibitors of protein kinase C) did not block thc AA-induced inhibition of I(Ca), and application of phorbol ester (a protein kinase C activator) (phorbol-12,13-dibutyrate, 0.2-mu-M) did not mimic the AA action. Some other cis-unsaturated fatty acids (palmitoleic, linoleic, and oleic acids) were also found to depress I(Ca), while a trans-unsaturated fatty acid (linolelaidic acid) and saturated fatty acids (capric, lauric, myristic, and palmitic acids) had no inhibitory effects on I(Ca). Myristic acid consistently increased the amplitude of I(Ca) at negative membrane potentials. The present results suggest the possible role of AA, and perhaps other fatty acids, in the physiological and/or pathological modulation of I(Ca) in smooth muscle.