Korean J Physiol Pharmacol.  1999 Jun;3(3):293-303.

Opening of ATP-sensitive K+ channel by pinacidil requires serine/threonine phosphorylation in rat ventricular myocytes

• Kwak YG
• Chae SW

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.

Keyword

Pinacidil; Phosphorylation; Dephosphorylation; KATP channel; Serine/thieonine; Tyiosine; Rat ventricular myocyte

MeSH Terms

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*
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Adenosine Triphosphate
Adenylyl Imidodiphosphate
Genistein
KATP Channels
Pinacidil
Protein Kinase Inhibitors
Protein Phosphatase 2
Protein Tyrosine Phosphatase, Non-Receptor Type 1