Effects of Na+channel isoforms and lipid membrane environment on temperature tolerance of cardiac Na+current in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss)

ABSTRACT Heat tolerance of heart rate in fish is suggested to be limited by impaired electrical excitation of the ventricle due to the antagonistic effects of high temperature on Na + (I Na ) and K + (I K1 ) ion currents (I Na is depressed at high temperatures while I K1 is resistant to them). To examine the role of Na + channel proteins and the lipid matrix of the channels in heat tolerance of I Na , we compared temperature-dependencies of zebrafish ( Danio rerio ) and rainbow trout ( Oncorhynchus mykiss ) ventricular I Na , and I Na generated by the cloned zebrafish and rainbow trout Na V 1.4 and Na V 1.5 Na + channels in HEK cells. Whole-cell patch clamp recordings showed that zebrafish ventricular I Na has better heat tolerance and slower inactivation kinetics than rainbow trout ventricular I Na . In contrast, heat tolerance and inactivation kinetics of zebrafish and rainbow trout Na V 1.4 channels are similar when expressed in the identical plasma membrane lipid matrix of HEK cells. The same applies to Na V 1.5 channels. Thermal adaptation of the ventricular I Na is largely achieved by differential expression of Na + channel alpha subunits: zebrafish which tolerate well high temperatures mainly express the slower Na V 1.5 isoform, while rainbow trout which prefer cold waters mainly express the faster Na V 1.4 isoform. Differences in elasticity (stiffness) of the lipid bilayer may be also involved in thermal adaptation of I Na . These findings suggest that both the protein component and its lipid bilayer matrix are involved in thermal adaptation of the voltage-gated Na + channels and therefore in heart rate regulation under thermal stress in fish.