Triggered propagated contractions in rat cardiac trabeculae. Inhibition by octanol and heptanol.
We studied the role of Ca2+ diffusion through gap junctions (GJs) in triggering and propagation of damage-induced contractions in cardiac muscle (TPCs) by evaluating effects of the GJ blockers octanol and heptanol (O&H) on TPCs. TPCs were elicited in trabeculae from rat right ventricle superfused with Krebs-Henseleit solution at 20 degrees C and 0.7 to 1.75 mmol/L [Ca2+]o. Force was measured with a silicon strain gauge; sarcomere length, by laser diffraction techniques. O&H (3 to 300 mumol/L) decreased force, propagation velocity, and triggering rate of TPCs in a dose-dependent manner. At 300 mumol/L, O&H decreased TPC force to 21.3% and 25.7%, propagation velocity to 15.4% and 13.0%, and triggering rate to 26.5% and 25.7%. At 300 mumol/L. O&H decreased twitch force to 79.0% and 77.8% and reduced time to 90% relaxation by 10% to 15%. Above 1 mmol/L, O&H abolished twitch force and TPCs. Image analysis of spread of the fluorescence profile of microinjected fura 2 salt revealed an effective diffusion coefficient for fura 2 of 21.0 +/- 3.3 microns2/s, which decreased to 12.6+/-1.5 and 7.07 +/- 0.7 microns2/s after 1 and 3 hours of exposure, respectively, to 100 mumol/L octanol, with a time constant of decline of 1.5+/-0.5 hours. These results are consistent with the hypothesis that propagation of TPCs is due to Ca(2+)-induced Ca2+ release mediated by Ca2+ diffusion from cell to cell through GJs. Reduction of propagation velocity reduces the number of activated sarcomeres in the TPC, which reduces TPC force. O&H slow triggering of TPCs, presumably by blocking Ca2+ diffusion from myocytes within damaged areas to adjacent normal cells.
Zhang
Y M
YM
Department of Medicine, University of Calgary, Canada.
Miura
M
M
ter Keurs
H E
HE
D000818:Animals; D002118:Calcium / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D000442:Octanols / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN
D000442:Octanols; D002118:Calcium