Korean Circ J.  2005 Nov;35(11):812-820. 10.4070/kcj.2005.35.11.812.

Modulation of Muscarinic K+ Channel by Protein Kinase C in Ischemic Rat Atrial Myocytes

• Kang D
• Lee HS
• Hong SG
• Han J

• KMID: 2297959
• DOI: http://doi.org/10.4070/kcj.2005.35.11.812

Abstract

BACKGROUND AND OBJECTIVES
Recent studies have shown that many kinds of K+ channels, including the muscarinic K+ channel (KACh), are activated in the ischemic heart. It is known that these channels can be modulated by phosphorylation. However, little is known about the function of the KACh in ischemic hearts. In this study, we examined whether the KACh channel is mediated by protein kinase C (PKC) activation in rat atrial myocytes under ischemic conditions.
MATERIALS AND METHODS
Single atrial cells of adult rat heart were prepared by collagenase digestion. Channel activity of KACh was recorded by cell-attached configuration from single atrial cells under ischemic conditions, using a patch clamp technique. To simulate ischemia, adenosine or potassium cyanide (KCN) was applied to atrial myocytes, and Western blot was performed to specify PKC isoforms.
RESULTS
Adenosine and KCN markedly increased KACh channel activity. The responses to adenosine and KCN were increased 3-fold at mean open time from that observed with control. Channel activity of KACh was blocked by pretreatment with PKC antagonists such as sphingosine, Go 6976, and rottlerin. PKC alpha and PKC betaI isoform levels were increased in the membrane fraction of ischemic heart, indicating that ischemic stress might trigger translocation of cytosolic PKC to the cell membrane.
CONCLUSION
These results show that KACh channels are modulated by PKC activation under ischemic conditions induced by adenosine or KCN. Therefore, the channels can protect the heart from ischemic stress by increasing channel activity.

Keyword

Ischemia; Adenosine; Potassium cyanide; GIRK; Protein kinase C

MeSH Terms

Adenosine
Adult
Animals
Blotting, Western
Cell Membrane
Collagenases
Cytosol
Digestion
Heart
Humans
Ischemia
Membranes
Muscle Cells*
Phosphorylation
Potassium Cyanide
Protein Isoforms
Protein Kinase C*
Protein Kinases*
Rats*
Sphingosine
Adenosine
Collagenases
Potassium Cyanide
Protein Isoforms
Protein Kinase C
Protein Kinases
Sphingosine