Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes.
OBJECTIVE
Brain-type alpha-subunit isoforms of the Na(+) channel are present in various cardiac tissue types and may control pacemaker activity and excitation-contraction coupling. Heart failure (HF) alters pacemaker activity and excitation-contraction coupling. Here, we studied whether HF alters brain-type Na(+) channel properties.


RESULTS
HF was induced in rabbits by volume/pressure overload. Na(+) currents of ventricular myocytes were recorded in the cell-attached mode of the patch-clamp technique using macropatches. Macropatch recordings were conducted from the middle portions of myocytes or from intercalated disc regions between cell pairs. Both areas exhibited a fast activating and inactivating current, 8.5 times larger in intercalated disc regions. Tetrodotoxin (TTX) (50 nM) did not block currents in the intercalated disc regions, but did block in the middle portions, indicating that the latter currents were TTX-sensitive brain-type Na(+) currents. Macropatch recordings from these regions were used to study the effects of HF on brain-type Na(+) current. Neither current density nor gating properties (activation, inactivation, recovery from inactivation, slow inactivation) differed between CTR and HF.


CONCLUSIONS
The density and gating properties of brain-type Na(+) current are not altered in our HF model. In the volume/pressure-overload rabbit model of HF, the role of brain-type Na(+) current in HF-induced changes in excitation-contraction coupling is limited.
Verkerk
Arie O
AO
Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van Ginneken
Antoni C G
AC
van Veen
Toon A B
TA
Tan
Hanno L
HL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels
D015222:Sodium Channels; D012964:Sodium