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1 Physiology, Loyola University Medical Center, Maywood, Illinois, United States
* To whom correspondence should be addressed. E-mail: dbers{at}lumc.edu.
The Na+/K+ATPase (NKA) is the main route for Na+extrusion from cardiac myocytes. Different NKA 
-subunit isoforms are present in the heart. NKA-1 is predominant although there is a variable amount of NKA-2 in adult ventricular myocytes of most species. It has been proposed that NKA-2 is localized mainly in T-tubules (TT), where they could regulate local Na+/Ca2+ exchange and thus cardiac myocyte Ca2+. However, there is controversy as to where NKA-1 vs. NKA-2 are localized in ventricular myocytes. Here, we assess the TT vs. external sarcolemma (ESL) distribution functionally using formamide-induced detubulation of rat ventricular myocytes, NKA current (IPump) measurements and the different ouabain sensitivity of NKA-1 (low) and NKA-2 (high) in rat heart. Ouabain-dependent IPump inhibition in control myocytes indicates a high affinity NKA isoform (NKA-2, K1/2=0.38±0.16 µM) that accounts for 29.5±1.3% of IPump and a low affinity isoform (NKA-1, K1/2=141±17 µM) that accounts for 70.5% of IPump. Detubulation decreased cell capacitance from 164±6 to 120±8 pF and reduced IPump density from 1.24±0.05 to 1.02±0.05 pA/pF, indicating that the functional density of NKA is significantly higher in TT vs. ESL. In detubulated myocytes, NKA-2 accounted for only 18.2±1.1% of IPump. Thus, ~63% of IPump generated by NKA-2 is from the TT (although TT are only 27% of the total sarcolemma) and the NKA-2/NKA-1 ratio in TT is significantly higher than in the ESL. The functional density of NKA-2 is ~4.5 times higher in the T-tubules vs. ESL whereas NKA-1 is almost uniformly distributed between the T-tubules and ESL.
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