The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C.
A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.
Varnum
M D
MD
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Busch
A E
AE
Bond
C T
CT
Maylie
J
J
Adelman
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D015698:Genomic Library; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D015221:Potassium Channels / Q000096:biosynthesis / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013873:Thionucleotides / Q000494:pharmacology
D010703:Phorbol Esters; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D013873:Thionucleotides; C059983:potassium channel protein I(sk); C008876:phorbol-12,13-didecanoate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007545:Isoproterenol