Effects of arachidonic acid (AA) and related fatty acids on Ca2+ -independent transient (A-type) K+ current (I(A)) were examined in single myocytes of guinea pig vas deferens, ureter, and proximal colon as well as in rabbit vas deferens. The peak amplitude of I(A) was reduced by external application of AA (half-maximal inhibitory concentration = approximately 1 microM). The blocking effect was not changed significantly by indomethacin, nordihydroguaiaretic acid, guanosine 5'-O-(2-thiodiphosphate), or guanosine 5'-O-(3-thiotriphosphate). Pharmacological studies suggested that the effect of AA was not mediated by activation of protein 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. I(A)-like current in cardiac atrial myocytes of the rabbit was not affected significantly by 30 microM 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+ channels in smooth muscle cells can be clearly resolved from those in atrial myocytes by the responses to AA.

A Na⁺/Ca²⁺ exchanger (NCX) is one of the major regulators of intracellular Ca²⁺ concentration ([Ca²⁺]_i) in cardiac muscle cells. Although vascular smooth muscle myocytes also express NCX proteins, their functional role has not been clear, mainly due to the lack of specific inhibitors of NCX and relatively low levels of expression of NCX. In the present study, we have examined the involvement of NCX in the Na⁺ deficient (0 Na⁺) elevation of [Ca²⁺]_i in rat carotid arterial myocytes using KB-R7943, an inhibitor of NCX. Perfusion with a Na⁺-free bathing solution, prepared by replacement of Na⁺ with N-methyl-D-glucamine, induced an elevation of [Ca²⁺]_i, which was effectively inhibited by KB-R7943 (IC₅₀=3.5 μM). This inhibition was reversed by washout of KB-R7943. In contrast, D600, a blocker of voltage dependent L-type Ca²⁺ channels (VDCC), did not affect the 0 Na⁺-induced elevation of [Ca²⁺]_i. Treatment of myocytes with ryanodine abolished the elevation of [Ca²⁺]_i caused by caffeine but not that caused by 0 Na⁺. Application of Cd²⁺, which is known to block NCX as well as VDCC, also significantly inhibited the 0 Na⁺ induced elevation. These results suggest that KB-R7943 inhibits the extracellular Na⁺ dependent ([Na⁺]_o) change in [Ca²⁺]_i in rat carotid arterial myocytes, which is presumably activated by the reverse mode of NCX.