Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes.
When expressed in the Xenopus oocyte, the minK protein induces a slowly activating voltage-dependent potassium current (Isk). We studied the modulation of this current by altering intracellular cAMP levels and found that the amplitude of Isk is dramatically increased by treatments that raise cAMP levels and decreased by agents that lower cAMP levels. Preinjection of a protein inhibitor of the cAMP-dependent protein kinase blocked the effects of increased cAMP levels. There were no changes in the voltage dependence or kinetics of Isk. Mutations that eliminate a potential phosphorylation site on the minK protein did not block the effects of activating the kinase. In addition, the membrane capacitance of the oocyte increased and decreased in parallel with Isk. Our results fit a mechanism in which channel proteins are selectively inserted into and removed from the plasma membrane in response to changes in kinase activity.
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06510.
E M
EM
Blumenthal
L K
LK
Kaczmarek
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011374:Progesterone / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012313:RNA / Q000235:genetics; D051381:Rats; D014162:Transfection; D014982:Xenopus laevis
D008565:Membrane Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D047428:Protein Kinase Inhibitors; C059983:potassium channel protein I(sk); D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D012313:RNA; D000242:Cyclic AMP; D011494:Protein Kinases