Growth and function of the embryonic heart depend upon the cardiac-specific L-type calcium channel alpha1 subunit.
The heart must function from the moment of its embryonic assembly, but the molecular underpinnings of the first heart beat are not known, nor whether function determines form at this early stage. Here, we find by positional cloning that the embryonic lethal island beat (isl) mutation in zebrafish disrupts the alpha1 C L-type calcium channel subunit (C-LTCC). The isl atrium is relatively normal in size, and individual cells contract chaotically, in a pattern resembling atrial fibrillation. The ventricle is completely silent. Unlike another mutation with a silent ventricle, isl fails to acquire the normal number of myocytes. Thus, calcium signaling via C-LTCC can regulate heart growth independently of contraction, and plays distinctive roles in fashioning both form and function of the two developing chambers.
Rottbauer
W
W
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Baker
K
K
Wo
Z G
ZG
Mohideen
M A
MA
Cantiello
H F
HF
Fishman
M C
MC
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001281:Atrial Fibrillation; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000502:physiology*; D015723:Gene Library; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D008854:Microscopy, Electron; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D015027:Zebrafish
D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D002118:Calcium