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Pflügers Archiv

, Volume 422, Issue 6, pp 617–619 | Cite as

Trypsin and α-chymotrypsin treatment abolishes glibenclamide sensitivity of KATP channels in rat ventricular myocytes

  • C. G. Nichols
  • A. N. Lopatin
Short Communication Excitable Tissues and Central Nervous Physiology

Abstract

Cytoplasmic trypsin-treatment of voltagesensitive potassium channels has been shown to cleave domains of the channel responsible for inactivation of the channel. Trypsin has also been reported to remove slow, irreversible inactivation, or run-down in ATP-sensitive potassium (KATP) channels. Cytoplasmic treatment of rat ventricular KATP channels with either crude, or pure trypsin (1–2 mg/ml) failed to prevent a slow run-down of channel activity. However, trypsin (porcine pancreatic type IX, or type II (Sigma Chem. Co.), or αchymotrypsin (Sigma Chem. Co.) rapidly and irreversibly removed, or substantially decreased glibenclamide and tolbutamide-sensitivity of the channels without removing sensitivity to ATP. We conclude that glibenclamide must bind to either a separate protein, or to a separate domain on the channel in order to effect channel inhibition, and this domain is functionally disconnected from the channel by trypsin-, or α-chymotrypsin treatment.

Key words

Glibenclamide Trypsin Chymotrypsin Adenosine triphosphate Sulfonylurea Potassium channel Metabolism Heart Cardiac ventricle 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • C. G. Nichols
    • 1
  • A. N. Lopatin
    • 1
  1. 1.Department of Cell Biology and PhysiologyWashington University, School of MedicineSt. LouisUSA

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