Korean J Physiol Pharmacol.  1998 Dec;2(6):743-753.

Modulation of ATP-induced activation of the muscarinic K+ channel activity by protein kinase C

• Kim YM
• Park HK
• Han JH
• Park CO
• Hong SG

Abstract

The atrial acetylcholine-activated K+ (KACh) channel is gated by the pertussis toxin-sensitive inhibitory G (GK) protein. Earlier studies revealed that ATP alone can activate the KACh channel via transphosphorylation mediated by nucleoside-diphosphate kinase (NDPK) in atrial cells of rabbit and guinea pig. This channel can be activated by various agonists and also modulated its function by phosphorylation. ATP-induced KACh channel activation (AIKA) was maintained in the presence of the NDPK inhibitor, suggesting the existence of a mechanism other than NDPK-mediated process. Here we hypothesized the phosphorylation process as another mechanism underlying AIKA and was undertaken to examine what kinase is involved in atrial cells isolated from the rat heart. Single application of 1 mM ATP gradually increased the activity of KACh channels and reached its maximum 40 ~ 50 sec later following adding ATP. AIKA was not completely reduced but maintained by half even in the presence of NDPK inhibitor. Neither ADP nor a non-hydrolyzable ATP analogue, AMP-PNP can cause AIKA, while a non-specific phosphatase, alkaline phosphatase blocked completely AIKA. PKC antagonists such as sphingosine or tamoxifen, completely blocked AIKA, whereas PKC catalytic domain increased AIKA. Taken together, it is suggested that the PKC-mediated phosphorylation is partly involved in AIKA.

Keyword

muscarinic K+channel; PKC; ATP; Phosphorylation; Atrial myocytes

MeSH Terms

Adenosine Diphosphate
Adenosine Triphosphate
Adenylyl Imidodiphosphate
Alkaline Phosphatase
Animals
Catalytic Domain
Guinea Pigs
Heart
Nucleoside-Diphosphate Kinase
Phosphorylation
Phosphotransferases
Protein Kinase C*
Protein Kinases*
Rats
Sphingosine
Tamoxifen
Whooping Cough
Adenosine Diphosphate
Adenosine Triphosphate
Adenylyl Imidodiphosphate
Alkaline Phosphatase
Nucleoside-Diphosphate Kinase
Phosphotransferases
Protein Kinase C
Protein Kinases
Sphingosine
Tamoxifen