Purinergic activation of a leak potassium current in freshly dissociated myocytes from mouse thoracic aorta

Acta Physiol (Oxf). 2009 Feb;195(2):247-58. doi: 10.1111/j.1748-1716.2008.01884.x. Epub 2008 Jul 30.

Abstract

Aim: Exogenous ATP elicits a delayed calcium-independent K(+) current on freshly isolated mouse thoracic aorta myocytes. We investigated the receptor, the intracellular pathway and the nature of this current.

Methods: The patch-clamp technique was used to record ATP-elicited delayed K(+) current in freshly dissociated myocytes.

Results: ATP-elicited delayed K(+) current was not inhibited by a 'cocktail' of K(+) channel blockers (4-AP, TEA, apamin, charybdotoxin, glibenclamide). The amplitude of the delayed K(+) current decreased after the reduction of extracellular pH from 7.4 to 6.5. These two characteristics suggest that this current could be carried by the TASK subfamily of 'twin-pore potassium channels' (K2P). Purinergic agonists including dATP, but not ADP, activated the delayed K(+) current, indicating that P2Y(11) is the likely receptor involved in its activation. The PKC activator phorbol ester 12,13-didecanoate stimulated this current. In addition, the PKC inhibitor Gö 6850 partially inhibited it. Real-time quantitative PCR showed that the genes encoding TASK-1 and TASK-2 are expressed.

Conclusion: Our results indicate that blocker cocktail-insensitive delayed K(+) current in freshly dissociated aortic myocytes is probably carried by the TASK subfamily of twin-pore channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Aorta, Thoracic
  • Apamin / pharmacology
  • Charybdotoxin / pharmacology
  • Gene Expression
  • Glyburide / pharmacology
  • Hydrogen-Ion Concentration
  • Indoles / pharmacology
  • Male
  • Maleimides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Muscle Cells / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Indoles
  • Kcnk5 protein, mouse
  • Maleimides
  • Nerve Tissue Proteins
  • Potassium Channel Blockers
  • Potassium Channels, Tandem Pore Domain
  • Charybdotoxin
  • potassium channel subfamily K member 3
  • Apamin
  • Adenosine Triphosphate
  • Protein Kinase C
  • bisindolylmaleimide I
  • Glyburide