Influence of postnatal-development on I-f occurrence and properties in neonatal rat ventricular myocytes

Objective: I-f is a hyperpolarization-activated current, which plays a key role in determining the spontaneous rate of cardiac pacemaker cells. We hav e previously shown that I-f is also expressed in left ventricular myocytes isolated from spontaneously hypertensive rats; in these cells, its occurren ce and density is linearly related with the severity of myocardial hypertro phy. Since hypertrophy induces a re-expression of genes encoding fetal prot eins, we investigated changes in I-f properties during post-natal developme nt. Methods: Fresh ventricular myocytes were enzymatically isolated from th e heart of 1-2- to 28-day-old Wister mts. The whole-cell configuration of t he patch-clamp technique was employed to record the action potential and I- f. Results: Membrane capacitance, an index of cell size, progressively incr eased from 13+/-1 pF at 1-2 days to 66+/-4 pF at 28 days of age (p<0.01). A t 1-2 days, a cesium-sensitive hyperpolarization-activated inward current ( I-f) was recorded in the majority of tested cells (n=51). The midpoint of t he activation curve (V-1/2) was -78+/-2 mV (n=32), and specific current con ductance of fully activated I-f (g(f,max)) was 60+/-11 pS/pF. Reversal pote ntial (V-rev) measured by tail-current analysis was -24+/-3 mV(n=8). Reduct ion of extracellular Na+ from 140 to 35 mM or extracellular K+ from 25 to 5 .4 mM caused a shift of -12+/-1 mV(n=3) or -11+/-2, mV(n=5) of V-rev, respe ctively. Occurrence of I-f decreased with aging, being present in 64%, 48% and 32% of cells at 10, 15 and 28 days, respectively. When present, I-f den sity was significantly smaller than at 1-2 days (p<0.05), reaching a value of 8+/-2 pS/pF at 28 days. However, V-1/2 did not change in the older rats, being -80+/-2, -83+/-4 and -85+/-3 mV at 10, 15 and 28 days, respectively. V-rev at 10 and 15 days was -27 and -28 mV,respectively, thus suggesting t hat channel selectivity did not change. Conclusions: The pacemaker current, I-f, is expressed in ventricular myocytes from neonatal rats and progressi vely disappears; when present, it shows electrophysiological properties sim ilar to I-f re-expressed in hypertrophied adult rat ventricular myocytes. T hus, it is likely that the occurrence of I-f in ventricular myocytes of hyp ertrophied and failing hearts is due to the re-expression of a fetal gene. (C) 1999 Elsevier Science B.V. All rights reserved.