Age-dependent changes in Na current magnitude and TTX-sensitivity in the canine sinoatrial node

In rabbit, sodium current (I_Na) contributes to newborn sinoatrial node (SAN) automaticity but is absent in adult SAN, where heart rate is slower. In contrast, heart rate is high and I_Na is functional in adult mouse SAN. Given the slower heart rates of large mammals, we asked if I_Na is functionally active in SAN of newborn or adult canine heart. SAN cells were isolated from newborn (6-10 days), young (40-43 days) and adult mongrels. I_Na was observed in > 80% of cells from each age. However, current density was markedly greater in newborn, decreasing with age. At all ages, I_Na was sensitive to nanomolar tetrodotoxin (TTX); 100 nmol/L inhibited I_Na by 46.7%, 59.9% and 90.7% in newborn, young and adult cells, respectively. While high TTX sensitivity suggested the presence of non-cardiac isoforms, steady-state inactivation was relatively negative (midpoints − 89.7 ± 0.7 mV, − 95.1 ± 1.2 mV and − 93.4 ± 1.9 mV from newborn to adult). Consequently, I_Na should be unavailable at physiological potentials under normal conditions, and 100 nmol/L TTX did not change cycle length or action potential parameters of spontaneous adult SAN cells. However, computer modeling predicts the large newborn I_Na protects against excess rate slowing from strong vagal stimulation. The results show that canine SAN cells have TTX-sensitive I_Na which decreases with post-natal age. The current does not contribute to normal automaticity in isolated adult cells but can be recruited to sustain excitability if nodal cells are hyperpolarized. This is particularly relevant in newborn, where I_Na is large and parasympathetic/sympathetic balance favors vagal tone.