The effect of amiloride and its analog dichlorobenzamil on the cardiac chronotropic responses of myocardial cell aggregates in culture to alterations of extracellular potassium or calcium.
1. Cardiac ventricular myocytes aggregates from 7-day-old chick embryos show a decrease in beating rate with increasing [K+]0, from 1 to 10 mM, and stop beating at 10 mM. 2. Amiloride, at 10(-7) and 10(-6) M, produced a significant (P less than 0.05) accentuation of the effects of increasing [K]0 that were dose dependent and produced an earlier cessation of spontaneous beating. 3. The amiloride analogue 3',4'-dichlorobenzamil (DCB), that preferentially inhibits Na+/Ca2+ exchange, produced a significant (P less than 0.05) accentuation of the effects of [K+]0 that were greater than that produced by amiloride. 4. When [Ca]0 was increased from 2.2 to 5.0 mM, cardiac beating rate increased, became irregular and then stopped at [Ca2+]0 of 5 mM. 5. DCB, but not amiloride, significantly (P less than 0.05) accentuated the changes with increasing [Ca2+]0. Thus inhibition of Na+-Ca2+ exchange accentuates the effect of increased [Ca]0 on the heart.
Rabkin
S W
SW
Cardiovascular Research Laboratories, University of British Columbia, Vancouver, Canada.
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D006339:Heart Rate / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*
C041470:3',4'-dichlorobenzamil; D000584:Amiloride; D011188:Potassium; D002118:Calcium