ELECTROPHYSIOLOGICAL EFFECTS OF LINOLENIC ACID ON RAT VENTRICULAR CARDIOMYOCYTES

Electrophysiological effects of linolenic acid on rat ventricular cell s were examined in this study. Short term (3 to 5 min) exposure to low er concentration of linolenic acid (4 to 16 mu M) caused reversible in hibition of action potential upstroke and prolongation of action poten tial duration (APD(50)). Exposure to a higher concentration of linolen ic acid (40 mu M) caused depolarization of resting membrane potential, but APD(50) was not further prolonged. Voltage clamp study revealed t hat the initial prolongation of APD(50) in rat ventricular cells was m ediated mainly by inhibition of 4-AP sensitive transient outward curre nt (I-to). In addition to the inhibition of I-to, a prominent initial inhibition of delayed rectifier and inward rectifier in guinea pig ven tricular cells was observed. After long term (greater than or equal to 10 min) exposure to linolenic acid, a prominent increase of barium se nsitive potassium outward current in guinea pig ventricular cells was observed. For cells bathed in low Na+ medium and internally dialyzed w ith cesium pipette solution, 3 to 5 min exposure 4 to 40 mu M linoleni c acid inhibited sodium inward current (I-Na) and calcium inward curre nt (I-Ca) reversibly and dose-dependently. The inhibition of I-Na, by linolenic acid was associated with left shift of its steady state inac tivation curve. IC50 for inhibition of I-Na was calculated to be 6.3 m u M IC50 For inhibition of I-Ca, however, was calculated to be 33.3 mu M when the spontaneous rundown of I-Ca was corrected. These results s uggest that short term exposure to linolenic acid may result in a simu ltaneous inhibition of sodium inward, calcium inward and potassium out ward current. Long term exposure to linolenic acid, however, may short en APD by an activation of fatty acid sensitive potassium channels or cause membrane depolarization by an increase of leakage current or red uction of potassium current through inward rectifier.