Thyroid Hormone Increases Pacemaker Activity in Rat Neonatal Atrial Myocytes

The effects of thyroid hormone (3,3′,5-triiodo- L -thyronine, T3) on pacemaker activity were studied with electrophysiological and pharmacological approaches using spontaneously beating neonatal atrial myocytes cultured from 2-day-old rats. Treatment with T3(10−8m) for 24–48 h led to a positive chronotropic effect. The beating rate of T3-treated cells was 244±19 beats/min and for control cells it was 122±10 beats/min (P<0.05). Action potentials were recorded and showed that the predominant effect of T3was to increase the diastolic depolarization rate (99.5±9.8 in T3-treated group v 44.0±7.8 mV/s in untreated group). Some cells that exhibited pacemaker activity lacked a pacemaker current (If) under voltage clamp conditions Ifwas recorded in 5 of 12 spontaneously active control cells and in 6 of 10 T3-treated cells. In those cells exhibiting the pacemaker current, the Ifdensity was significantly larger in T3-treated cells (−7.9±2.6 pA/pF v−1.8±0.5 pA/pF in control). The L-type Ca2+current density was similar in the two groups (at −7 mV, −7.5±1.5 in treated groupv −8.6±1.0 pA/pF in control). In the presence of T3, the Na+–Ca2+exchanger current (INa/Ca) density was larger (e.g. at +60 mV, it was 4.8±0.5 v 3.5±0.2 pA/pF in control cells, P<0.05). As intracellular Ca2+is extruded from the cell, the electrogenic Na+–Ca2+exchanger causes a declining inward current, which may contribute to the pacemaker potential—this declining inward current was demonstrated using the action potential voltage clamp technique and was shown to be larger in T3-treated myocytes. Our data demonstrate that thyroid hormone enhances pacemaker activity and that this may be due in part to an increased Na+–Ca2+exchanger activity.