The slow mo mutation reduces pacemaker current and heart rate in adult zebrafish.
Genetic studies in zebrafish have focused on embryonic mutations, but many physiological mechanisms continue to mature after embryogenesis. We report here that zebrafish homozygous for the mutation slow mo can be raised to adulthood. In the embryo, the slow mo gene is needed to regulate heart rate, and its mutation causes a reduction in pacemaker current (I(h)) and slowing of heart rate (bradycardia). The homozygous adult slow mo fish continues to manifest bradycardia, without other evident ill effects. Patch-clamp analysis of isolated adult cardiomyocytes reveals that I(h) has chamber-specific properties such that the atrial current density of I(h) is far greater than the ventricular current density of I(h). I(h) is markedly diminished in cardiomyocytes from both chambers of slow mo mutant fish. Thus I(h) continues to be a critical determinant of pacemaker rate even after adult neural and humoral influences have developed. It is clear that zebrafish may be used for genetic dissection of selected physiological mechanisms in the adult.
Warren
K S
KS
Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Baker
K
K
Fishman
M C
MC
D000818:Animals; D016275:Atrial Function; D001919:Bradycardia / Q000235:genetics / Q000503:physiopathology; D002478:Cells, Cultured; D004594:Electrophysiology; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D009154:Mutation / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D015222:Sodium Channels / Q000502:physiology; D016276:Ventricular Function; D015027:Zebrafish / Q000235:genetics*
D015222:Sodium Channels