EFFECTS OF ARACHIDONIC-ACID ON A-TYPE POTASSIUM CURRENTS IN SMOOTH-MUSCLE CELLS OF THE GUINEA-PIG

Effects of arachidonic acid (AA) and related fatty acids on Ca2+-indep endent transient (A-type) K+ current (I-A) were examined in single myo cytes of guinea pig vas deferens, ureter, and proximal colon as well a s in rabbit vas deferens. The peak amplitude of I-A was reduced by ext ernal application of AA (half-maximal inhibitory concentration = simil ar to 1 mu M). The blocking effect was not changed significantly by in domethacin, nordihydroguaiaretic acid, guanosine 5'-O-(2-thiodiphospha te), or guanosine 5'-O-(3-thiotriphosphate). Pharmacological studies s uggested that the effect of AA was not mediated by activation of prote in kinases A or C or tyrosine kinase. AA (20:4) was the most potent of the four types of cis-eicosanoic acids with two to five double bonds (20:2 to 20:5)that were tested. IA-like current in cardiac atrial myoc ytes of the rabbit was not affected significantly by 30 mu M AA. These results indicate that AA itself directly blocks A-type K+ channels. A relationship between stereospecific chemical structure of fatty acids and their blockade of A-type K+ channels is suggested. A-type K+ chan nels in smooth muscle cells can be clearly resolved from those in atri al myocytes by the responses to AA.