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+ -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.
Nagano
N
N
Department of Chemical Pharmacology, Faculty of Pharmacological Science, Nagoya City University, Nagoya, Japan.
Imaizumi
Y
Y
Watanabe
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D003106:Colon / Q000502:physiology; D004553:Electric Conductivity; D005227:Fatty Acids / Q000494:pharmacology; D005609:Free Radicals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D014513:Ureter / Q000502:physiology; D014649:Vas Deferens / Q000502:physiology
D005227:Fatty Acids; D005609:Free Radicals; D015221:Potassium Channels; D016718:Arachidonic Acid; D013482:Superoxide Dismutase; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D011188:Potassium