OMEGA-3 POLYUNSATURATED FATTY-ACIDS - MODULATION OF VOLTAGE-DEPENDENTL-TYPE CA2-PIG TRACHEAL SMOOTH-MUSCLE CELLS( CURRENT IN GUINEA)

omega-3 polyunsaturated fatty acids have been reported to be associate d with favorable changes in the respiratory system. To determine one o f the mechanisms for this effect, membrane currents were recorded in g uinea-pig tracheal myocytes by using the whole-cell voltage clamp tech nique. Without EGTA in the patch pipette containing the Cs-internal so lution, command voltage pulses positive to +0 mV from a holding potent ial of -60 mV elicited a voltage-dependent L-type Ca2+ current (I-Ca . L) and a subsequent outward current. Upon repolarization, slowly deca ying inward tail currents were recorded. The outward currents and the inward tail current were enhanced by 4-(2-trigluromethylphenyl)-pyridi ne-5-carboxylate, and blocked by Cd2+ or nifedipine. Inclusion of EGTA (5 mM) in the patch pipette also abolished these currents, indicating that they were Ca2+-dependent. When [Cl-](o) or [Cl-](i) was changed, the reversal potential of these currents shifted, thus behaving like a Cl--sensitive ion channel. 4,8-Diisothiocyanatostilbene-2,2'-disulph onic acid, a Cl- channel blocker, inhibited the currents. The omega-3 polyunsaturated fatty acids eicosapentaenoic acid (3-30 mu M) and doco sahexaenoic acid (30 mu M) suppressed I-Ca . L and then inhibited I-Ca . Cl in a reversible manner. Similar inhibitory effects of eicosapent aenoic acid on I-Ca . L were observed with 5 mM EGTA in the patch pipe tte. Neurokinin A (1 mu M) and caffeine (10 mM) also transiently activ ated I-Cl . Ca, probably due to Ca2+ release from Ca2+ storage sites. Pretreatment of the cells with eicosapentaenoic acid markedly suppress ed the activation of I-Cl . Ca by neurokinin A or caffeine. These resu lts suggest that omega-3 polyunsaturated fatty acids inhibit voltage-d ependent L-type Ca2+ currents and also Ca2+-activated Cl- currents in tracheal smooth muscle cells from the guinea-pig, which may play a rol e in modulation of tracheal smooth muscle tone. (C) 1998 Elsevier Scie nce B.V. All rights reserved.