Characterization and influence of cardiac background sodium current in the atrioventricular node

Background inward sodium current (I-B,I-Na) that influences cardiac pacemaking has been comparatively under investigated. The aim of this study was to determine for the first time the properties and role of IB,Na in cells from the heart's secondary pacemaker, the atrioventricular node (AVN). Myocytes were isolated from the AVN of adult male rabbits and mice using mechanical and enzymatic dispersion. Background current was measured using whole-cell patch clamp and monovalent ion substitution with major voltage- and time-dependent conductances inhibited. In the absence of a selective pharmacological inhibitor of IB,Na, computer modelling was used to assess the physiological contribution of IB,Na. Net background current during voltage ramps was linear, reversing close to 0 mV. Switching between Tris- and Na+-containing extracellular solution in rabbit and mouse AVN cells revealed an inward I-B,I-Na, with an increase in slope conductance in rabbit cells at - 50 mV from 0.54 +/- 0.03 to 0.91 +/- 0.05 nS (mean +/- SEM; n = 61 cells). I-B,I-Na magnitude varied in proportion to [Na+](o). Other monovalent cations could substitute for Na+ (Rb+ > K+ > Cs+ > Na+ > Li+). The single-channel conductance with Na+ as charge carrier estimated from noise-analysis was 3.2 +/- 1.2 pS (n = 6). Ni2+ (10 mM), Gd3+ (100 mu M), ruthenium red (100 mu M), or amiloride (1 mM) produced modest reductions in I-B,I-Na. Flufenamic acid was without significant effect, whilst La3+ (100 mu M) or extracellular acidosis (pH 6.3) inhibited the current by >60%. Under the conditions of our AVN cell simulations, removal of I-B,I-Na arrested spontaneous activity and, in a simulated 1D-strand, reduced conduction velocity by similar to 20%. I-B,I-Na is carried by distinct low conductance monovalent nonselective cation channels and can influence AVN spontaneous activity and conduction. (C) 2016 The Authors. Published by Elsevier Ltd.