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

I(f) is a hyperpolarization-activated current, which plays a key role in determining the spontaneous rate of cardiac pacemaker cells. We have previously shown that I(f) is also expressed in left ventricular myocytes isolated from spontaneously hypertensive rats; in these cells, its occurrence and density is linearly related with the severity of myocardial hypertrophy. Since hypertrophy induces a re-expression of genes encoding fetal proteins, we investigated changes in I(f) properties during post-natal development.

Fresh ventricular myocytes were enzymatically isolated from the heart of 1-2- to 28-day-old Wistar rats. The whole-cell configuration of the patch-clamp technique was employed to record the action potential and I(f).

Membrane capacitance, an index of cell size, progressively increased from 13 +/- 1 pF at 1-2 days to 66 +/- 4 pF at 28 days of age (p < 0.01). At 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 the activation curve (V1/2) was -78 +/- 2 mV (n = 32), and specific current conductance of fully activated I(f) (gf.max) was 60 +/- 11 pS/pF. Reversal potential (Vrev) measured by tail-current analysis was -24 +/- 3 mV (n = 8). Reduction 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 Vrev, respectively. 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) density was significantly smaller than at 1-2 days (p < 0.05), reaching a value of 8 +/- 2 pS/pF at 28 days. However, V1/2 did not change in the older rats, being -80 +/- 2, -83 +/- 4 and -85 +/- 3 mV at 10, 15 and 28 days, respectively. Vrev at 10 and 15 days was -27 and -28 mV, respectively, thus suggesting that channel selectivity did not change.

The pacemaker current, I(f), is expressed in ventricular myocytes from neonatal rats and progressively disappears; when present, it shows electrophysiological properties similar to I(f) re-expressed in hypertrophied adult rat ventricular myocytes. Thus, it is likely that the occurrence of I(f) in ventricular myocytes of hypertrophied and failing hearts is due to the re-expression of a fetal gene.