Accession Number:

ADA274875

Title:

Effects of Potassium Channel Blockers on the Negative Inotropic Responses Induced by Cromakalim and Pinacidil in Guinea Pig Atrium

Descriptive Note:

Corporate Author:

DEFENCE SCIENCE AND TECHNOLOGY ORGANISATION CANBERRA (AUSTRALIA)

Personal Author(s):

Report Date:

1992-01-01

Pagination or Media Count:

12.0

Abstract:

The K channel openers cromakalim and pinacidil induced a concentration-dependent reduction in atrial contraction force with EC50 values of 25 - 2 and 37 - 2 micromoll, respectively. This depressant effect was antagonised by 50 micromall tacrine which displaced the concentration-response curves of cromakalim and pinacidil to the right. The respective DR50 values were 3.8 and 2.3. Increasing the tacrine concentration 100 and 500 micromoll produced no additional effect on the concentration-response relationships. Addition of 1 micromoll atropine enhanced the antagonism due to tacrine by increasing the DR50 value from 3.8 to 6.5 for cromakalim and from 2.3 to 5.2 for pinacidil. Glibenclamide, an ATP-sensitive K channel blocker, competitively inhibited the negative inotropic effects of cromakalim and pinacidil. The respective dissociation constants for glibenclamide against cromakalim and pinacidil were 0.57 and 0.35 Micromoll. Neither apamin nor variation in external Ca2 concentration affected the negative inotropic effects of the K channel openers. It was suggested that the mechanical effects of cromakalim and pinacidil are mediated through the ATP-sensitive K channels in the heart

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Pharmacology
  • Organic Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE