Effects of charged amphiphiles on cardiac cell contractility are mediated via effects on Ca2+ current.
Exposure of isolated adult rabbit myocytes to the negatively charged amphiphile dodecylsulfate (DDS; 10 microM) increased the contraction amplitude to 185% of control. The positively charged amphiphile dodecyltrimethylammonium (DDTMA; 10 microM) decreased the amplitude to 58%. DDS increased Ca2+ uptake by the same cells, but this uptake was partially prevented by nifedipine. DDTMA had no effect on Ca2+ uptake. Ca2+ binding to isolated sarcolemma of neonatal heart cells was increased by 10 microM DDS and, at higher concentrations, reduced by DDTMA. Single-cell voltage-clamp studies, using isolated rabbit myocytes, showed that DDS enhanced L-type Ca2+ currents (ICa,L), whereas DDTMA depressed ICa,L. DDS shifted current-voltage (I-V) and isochronal inactivation curves of ICa,L in the negative direction, whereas DDTMA shifted them in positive direction. Furthermore, DDS depressed T-type Ca2+ currents (ICa,T), and DDTMA enhanced ICa,T. The inotropic effects of the amphiphiles are therefore mediated to a significant degree by ICa,L. The shifts in the I-V and inactivation curves of ICa,L and the effect on ICa,T can be explained by changes in the actual membrane potential (Em), induced by the insertion of the amphiphiles in the outer monolayer of the sarcolemma. However, the changes in the Em do not explain the effect on the maximal current, indicating effects on the channel per se, possibly by an alteration of the lipid environment.
Post
J A
JA
Department of Medicine and Physiology, University of California, School of Medicine, Los Angeles 90024-1760.
Ji
S
S
Leonards
K S
KS
Langer
G A
GA
D000200:Action Potentials; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D004594:Electrophysiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D011188:Potassium / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D012508:Sarcolemma / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000644:Quaternary Ammonium Compounds; D019831:Sodium-Calcium Exchanger; D012967:Sodium Dodecyl Sulfate; C028913:dodecyl sulfate; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; C021838:sodium-translocating ATPase; D000252:Calcium-Transporting ATPases; C022806:dodecyltrimethylammonium; D011188:Potassium; D002118:Calcium