Learn More
Ventricular pacemaker current (I(f)) shows distinct voltage dependence as a function of age, activating outside the physiological range in normal adult ventricle, but less negatively in neonatal ventricle. However, heterologously expressed HCN2 and HCN4, the putative molecular correlates of ventricular I(f), exhibit only a modest difference in activation(More)
Background. - We have established proliferating human cardiomyocyte cell lines derived from non-proliferating primary cultures of adult ventricular heart tissue, using a novel method that may be applicable to many post-mitotic primary cultures. Methods and results. - Primary cells from human ventricular tissue, were fused with SV40 transformed, uridine(More)
In rabbit, sodium current (I(Na)) contributes to newborn sinoatrial node (SAN) automaticity but is absent in adult SAN, where heart rate is slower. In contrast, heart rate is high and I(Na) is functional in adult mouse SAN. Given the slower heart rates of large mammals, we asked if I(Na) is functionally active in SAN of newborn or adult canine heart. SAN(More)
normal physiology and pathophysiology of the heart extends beyond the beat-to-beat regulation of rate and contractile force arising from acute exposure to neurally released norepinephrine (NE). For example, postinfarction arrhythmias have been ascribed to nerve sprouting and excess sympathetic innervation (7). In addition, congenital arrhythmias in a German(More)
To test the hypothesis that the Ca(2+) channel blocker mibefradil slows heart rate due to inhibition of T-type Ca(2+) current in pacemaker cells, we studied effects of mibefradil on action potentials and ionic currents of isolated rabbit sinus node cells using the patch clamp technique. Mibefradil (100 nM and 1 microM) reduced spontaneous rate, decreased(More)
Although the neonatal sinus node beats at a faster rate than the adult, when a sodium current (I(Na)) present in the newborn is blocked, the spontaneous rate is slower in neonatal myocytes than in adult myocytes. This suggests a possible functional substitution of I(Na) by another current during development. We used ruptured [T-type calcium current(More)
The developmental increase in L-type Ca current (I(Ca,L)) density in the rat ventricle is reproduced in vitro by culturing neonatal myocytes with sympathetic neurons. We tested whether this effect of sympathetic innervation results from a chronic or sustained action of neurally released neuropeptide Y (NPY). Ventricular myocytes from newborn rats were(More)
The therapeutic success of human stem cell-derived cardiomyocytes critically depends on their ability to respond to and integrate with the surrounding electromechanical environment. Currently, the immaturity of human cardiomyocytes derived from stem cells limits their utility for regenerative medicine and biological research. We hypothesize that biomimetic(More)
Cell culture studies demonstrate an increase in cardiac L-type Ca2+ current (ICa,L) density on sympathetic innervation in vitro and suggest the effect depends on neurally released neuropeptide Y (NPY). To determine if a similar mechanism contributes to the postnatal increase in ICa,L in vivo, we prepared isolated ventricular myocytes from neonatal and adult(More)
Previous observations show that β-adrenergic modulation of pacemaker current (I(f)) in sinoatrial node (SAN) cells is impaired by disruption of normal Ca(2+)-homeostasis with ryanodine or BAPTA. Recently, the presence of Ca(2+)-activated adenylyl cyclase (AC) 1 was reported in SAN, and was proposed as a possible mechanism of Ca(2+)-dependence of(More)