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


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 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ashcroft SJH and Ashcroft FM (1990) Properties and functions of ATP-sensitive K-channels. Cell Signal 2: 197–214.Google Scholar
  2. 2.
    Ashford MLJ, Boden PR and Treherne JM (1990). Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP-K+ channels. Brit J Pharm 101:531–540.Google Scholar
  3. 3.
    Bernardi H, Fosset M. and Lazdunski M. (1992) ATP/ADP binding sites are present in the sulfonylurea binding protein associated with brain ATP-sensitive K+ channels. Biochemistry 31: 6328–6332.Google Scholar
  4. 4.
    Furukawa T, Zheng F. and Hiraoka M. (1992). Proteolytic digestion with trypsin prevents ‘run-down’ of ATP-sensitive K+ channel. Biophysical Journal 61: A249.Google Scholar
  5. 5.
    Hoshi T, Zagotta WN and Aldrich RW (1990). Biophysical and molecular mechanisms of Shaker Potassium Channel Inactivation. Science 250: 533–538.Google Scholar
  6. 6.
    Lederer WJ and Nichols CG. (1989) Nucleotide modulation of the activity of rat heart KATP channels in membrane patches. J Physiol (Lond) 419: 193–211.Google Scholar
  7. 7.
    Proks P and Ashcroft FM (1992). The effects of trypsin on ATPregulated K+ channels from pancreatic β-cells isolated from the mouse. J Physiol (Lond) (Abst. In Press).Google Scholar
  8. 8.
    Ripoll C, Lederer WJ and Nichols CG. (1992) On the mechanism of inhibition of KATP channels by glibenclamide in rat ventricular myocytes. J Cardiovasc Electrophys (In Press).Google Scholar

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

Personalised recommendations