© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Influence of postnatal-development on If occurrence and properties in neonatal rat ventricular myocytes
Department of Preclinical and Clinical Pharmacology, University of Firenze, Firenze, Italy
mugelli{at}pharm.unifi.it
* Corresponding author. Tel.: +39-055-427-1264; fax: +39-055-427-1285
Objective: If is a hyperpolarization-activated current, which plays a key role in determining the spontaneous rate of cardiac pacemaker cells. We have previously shown that If 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 If properties during post-natal development. Methods: 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 If. Results: 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 (If) 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 If (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 If decreased with aging, being present in 64%, 48% and 32% of cells at 10, 15 and 28 days, respectively. When present, If 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. Conclusions: The pacemaker current, If, is expressed in ventricular myocytes from neonatal rats and progressively disappears; when present, it shows electrophysiological properties similar to If re-expressed in hypertrophied adult rat ventricular myocytes. Thus, it is likely that the occurrence of If in ventricular myocytes of hypertrophied and failing hearts is due to the re-expression of a fetal gene.
KEYWORDS Cm, membrane capacitance; [K+]o, extracellular potassium concentration; (gf,max) gf, (maximal) specific conductance of If; [Na+]o, extracellular sodium concentration; V1/2, voltage of half maximal activation of If; Vrev, reversal potential of If.
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