A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel.
We studied the blocking mechanism of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the ATP-sensitive K+ channel in the single ventricular myocytes using the inside-out patch clamp technique. The channel activity in response to 5-hydroxydecanoate varied with each membrane patch corresponding to the sensitivity to ATP. In this condition the exogenous application of cAMP or cAMP-dependent protein kinase (PKA) obviously recovered the ATP-sensitive K+ channel activity after channel deactivation. By contrast, in membrane patches exhibited low sensitivity to ATP, endogenous cAMP-dependent protein kinase inhibitor (PKI) depressed the channel activity and restored the inhibitory action of 5-hydroxydecanoate and ATP on the channel. These results suggest that PKA-PKI system is involved in the regulatory mechanism of gating activity of the ATP-sensitive K+ channel and the blocking action of 5-hydroxydecanoate and ATP appears to be exerted by potentiating the inhibitory action of PKI on the channel.
Notsu
T
T
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Tanaka
I
I
Mizota
M
M
Yanagibashi
K
K
Fukutake
K
K
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D003652:Decanoic Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D006880:Hydroxy Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011494:Protein Kinases / Q000494:pharmacology / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D002352:Carrier Proteins; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006880:Hydroxy Acids; D047908:Intracellular Signaling Peptides and Proteins; D015221:Potassium Channels; C015482:protein kinase modulator; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases