Properties and modulation of If in newborn versus adult cardiac SA node.
The hearts in newborn mammals have greater intrinsic beating rates, rates of diastolic depolarization, and sensitivity to autonomic stimulation than those in adults. The differences could be explained partly by altered properties of the hyperpolarization-activated current (If). To test this possibility, sinoatrial node myocytes from the hearts of newborn (9- to 10-day) and adult (>30-day) rabbits were isolated, and the If was examined with the perforated-patch-clamp technique. The fully activated current-voltage relationship yielded a larger slope conductance of If in newborn SA node myocytes (0.244 +/- 0.020 vs. 0.158 +/- 0.012 pS/pF), compatible with the more rapid diastolic depolarization. Activation curves of the If had similar midactivation voltages (newborn, -66.71 +/- 1.94 mV; adult, -66.33 +/- 2.60 mV), but the slope was significantly greater in newborns (inverse slope factor: newborn, -9.57 +/- 0.35 mV; adult, -11.34 +/- 0.54 mV). No differences in shifts of the If activation curve in response to maximal concentrations of acetylcholine (newborn, -9.70 +/- 1.8 mV; adult, -12.60 +/- 2.10 mV) and isoproterenol (newborn, 6.90 +/- 2.5 mV; adult, 5.3 +/- 1.5 mV) or in the total shift in response to these agonists (newborn, 16.60 +/- 3.30 mV; adult, 18.00 +/- 1.00 mV) were observed. The greater If density and steeper voltage dependence can contribute to both the greater heart rate and the greater sensitivity of the SA node to autonomic modulation in newborn animals.
Accili
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Università di Milano, Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, Milan, Italy.
Robinson
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DiFrancesco
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D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003971:Diastole; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
D007545:Isoproterenol; D000109:Acetylcholine