Developmental changes in hyperpolarization-activated currents Ih and IK(IR) in isolated rat intracardiac neurons
The hyperpolarization-activated nonselective cation current, Ih, was investigated in neonatal and adult rat intracardiac neurons. Ih was observed in all neurons studied and displayed slow time-dependent rectification. Ih was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of Ih was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of Ih was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, IK(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. IK(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. IK(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. IK(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of IK(IR).IK(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in Ih may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.