Effects of charged amphiphiles on cardiac cell contractility are mediated via effects on Ca2+ current

Abstract

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.

Acute Enhancement of Synaptic Transmission and Chronic Inhibition of Synaptogenesis Induced by Perfluorooctane Sulfonate through Mediation of Voltage-Dependent Calcium Channel

“…There is evidence that alterations in membrane properties have a considerable impact on its various functions and substructures (23). In the present study we found that PFOS evidently augmented ICa ( Figure 3E) and significantly shifted the I -V curves of ICa in the negative direction ( Figures 3D and S4A), consistent with previous reports (14,24). Together with calcium imaging experiments ( Figures 4C and 4D), our findings indicated that the PFOS-induced increase in ICa was mainly mediated by L-type calcium channel.…”

“…PFOS has a sulfonic group attached to the perfluorinated chain, and PFOA has a carboxylic group. PFOS is likely to become incorporated into the lipid bilayer of the cell membrane (24), which may explain the differential effects of the two compounds on the Ca 2+ channels (Figure 3). In contrast to PFOS and PFOA, PFOC is an uncharged perfluorinated compound.…”

Changes in Synaptic Transmission, Calcium Current, and Neurite Growth by Perfluorinated Compounds Are Dependent on the Chain Length and Functional Group

“…The eight-carbon-chained (C-8) OA is an anionic surfactant which can be converted to PFOA when all the hydrogen atoms in its aliphatic chain are substituted by fluorine. When comparing the effects of OA and PFOA on cultured neurons, it was found that OA showed an insignificant increase of the mPSC frequency but evidently elevated the amplitude of I Ca ( Figures 1B and 2C) indicating that the surface activities of OA (similar to the PFCs) can interfere with the physiological processes of neurons, which is in agreement with past studies on other negatively charged surfactants (13,24). The same but more observable trends were observed on neurons with PFOA ( Figures 1B and 2C).…”

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

“…There are controversies in the literature regarding how cell swelling can modulate cardiac I Ca,L channel. For example, I Ca,L increases in neonatal rat ventricular myocytes [14] and rabbit sinoatrial node and atrial cells [12,13] , remains unaltered in canine ventricular myocytes [17] , decreases or remains unaltered in guinea-pig ventricular myocytes [10,15] . Brette et al had reported that in rat ventricular myocytes osmotic swelling decreases I Ca,L [16] .…”

“…However, the effect of cell swelling on cardiac I Ca,L remains controversial. For example, some studies have shown clear increases in I Ca,L [12][13][14] , while others have shown a decrease in I Ca,L [15,16] or no effect [10,17] . Some authors have even demonstrated biphasic effects on I Ca,L , an increase followed by a more sustained decrease [18] .…”