Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was inves tigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h w as isolated by blockade with external Cs+ (2 mM) and was inhibited irrevers ibly by the bradycardic agent, ZD 7288. Current density of I-h was approxim ately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as c ompared with adult (-2.3 pA/pF) rats; however, the reversal potential and a ctivation parameters were unchanged. The reversal potential and amplitude o f I-h was sensitive to changes in external Na+ and K+ concentrations. An in wardly rectifying K+ current, I-K(IR), was also present in intracardiac neu rons from adult but not neonatal rats and was blocked by extracellular Ba2. I-K(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. I-K(IR) d isplayed rapid activation kinetics and no time-dependent rectification cons istent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K +, whereby raising the external K+ concentration from 3 to 15 mM shifted th e reversal potential by approximately +36 mV. Substitution of external Nahad no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) de nsity increases as a function of postnatal development in a population of r at intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adu lt versus neonatal rat intracardiac ganglia.