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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.

Aggregation of acidic phospholipid vesicles induced by monovalent cations was studied for vesicles of small and large sizes. It was found that there were two phases in the aggregation of large acidic phospholipid vesicles. In the initial phase, observed in the range of 0.1-0.4 M monovalent salts, aggregation took place spontaneously after a change in salt concentration; in the second phase (greater than 0.4 M salt), aggregation progressed gradually with time. The order of capability for monovalent cations to induce the initial phase of aggregation of large phosphatidylserine vesicles (more than 1000 A in diameter) was Li+ greater than Na+ greater than K+ greater than TEA+. However, for the second phase of aggregation, the order was Na+ greater than Li+ greater than K+ greater than TEA+, which was the same as that to induce massive aggregation of small phosphatidylserine vesicles (250 A in diameter). A similar reversal in the order was observed in studies of the surface potential of the phosphatidylserine monolayer. In these studies, the order of the binding strength of monovalent cations was deduced from the change in surface potential produced by successive additions of MgCl2 to the subphase solution, which contained a certain level of monovalent salt initially. These measurements were carried out with monolayers that had a range of areas per molecule. The order was Na+ greater than Li+ greater than K+ for monolayers of large area (greater than 80 A2) per molecule and was Li+ greater than Na+ greater than K+ for those of small area (less than 80 A2) per molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

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