Opening of ATP-sensitive K+ channel by pinacidil requires serine/threonine phosphorylation in rat ventricular myocytes.
- Author:
Yong Geun KWAK
1
;
Soo Wan CHAE
Author Information
1. Department of Pharmacology, Chonbuk National University Medical School, Chonju, 560-182 South Korea.
- Publication Type:Original Article
- Keywords:
Pinacidil;
Phosphorylation;
Dephosphorylation;
KATP channel;
Serine/thieonine;
Tyiosine;
Rat ventricular myocyte
- MeSH:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine;
Adenosine Triphosphate;
Adenylyl Imidodiphosphate;
Animals;
Genistein;
KATP Channels;
Muscle Cells*;
Phosphorylation*;
Pinacidil*;
Protein Kinase Inhibitors;
Protein Phosphatase 2;
Protein Tyrosine Phosphatase, Non-Receptor Type 1;
Rats*
- From:The Korean Journal of Physiology and Pharmacology
1999;3(3):293-303
- CountryRepublic of Korea
- Language:English
-
Abstract:
The influences of specific protein phosphatase and protein kinase inhibitors on the ATP-sensitive K+ (KATP) channel-opening effect of pinacidil were investigated in single rat ventricular myocytes using patch clamp technique. In cell-attached patches, pinacidil (100 muM) induced the opening of the KATP channel, which was blocked by the pretreatment with H-7 (100 muM) whereas enhanced by the pretreatment with genistein (30 muM) or tyrphostin A23 (10 muM). In inside-out patches, pinacidil (10 muM) activated the KATP channels in the presence of ATP (0.3 mM) or AMP-PNP (0.3 mM) and in a partial rundown state. The effect of pinacidil (10 muM) was not affected by the pretreatment with protein tyrosine phosphatase 1B (PTP1B, 10 mug ml-1), but blocked by the pretreatment of protein phosphatase 2A (PP2A, 1 U ml-1). In addition, pinacidil (10 muM) could not induce the opening of the reactivated KATP channels in the presence of H-7 (100 muM) but enhanced it in the presence of ATP(1 mM) and genistein (30 muM). These results indicate that the KATP channel-opening effect of pinacidil is not mediated via phosphorylation of KATP channel protein or associated protein, although it still requires the phosphorylation of serine/threonine residues as a prerequisite condition.
