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

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 ) and K (I ) ion currents (I is depressed at high temperatures while I is resistant to them). To examine the role of Na channel proteins in heat tolerance of I , we compared temperature-dependencies of zebrafish ( warm-dwelling subtropical species) and rainbow trout ( cold-active temperate species) ventricular I , and I generated by the cloned zebrafish and rainbow trout Na 1.4 and Na 1.5 Na channels in HEK cells. Whole-cell patch clamp recordings showed that zebrafish ventricular I has better heat tolerance and slower inactivation kinetics than rainbow trout ventricular I In contrast, heat tolerance and inactivation kinetics of zebrafish and rainbow trout Na 1.4 channels are similar when expressed in the identical cellular environment of HEK cells. The same applies to Na 1.5 channels. These findings indicate that thermal adaptation of ventricular I is largely achieved by differential expression of Na channel alpha subunits: zebrafish which tolerate higher temperatures mainly express the slower Na 1.5 isoform, while rainbow trout which prefer cold waters mainly express the faster Na 1.4 isoform. Differences in elasticity (stiffness) of the lipid bilayer and/or accessory protein subunits of the channel assembly may be also involved in thermal adaptation of I The results are consistent with the hypothesis that slow Na channel kinetics are associated with increased heat tolerance of cardiac excitation.