Atrioventricular conduction and arrhythmias at the initiation of beating in embryonic mouse hearts.
To investigate cardiac physiology at the onset of heart beating in embryonic mouse hearts, we performed optical imaging of membrane potential (Vm) and/or intracellular calcium (Ca(i)). Action potentials and Ca(i) transients were detected in approximately 50% of mouse embryo hearts at E8.5, but in all hearts at E9.0, indicating that beating typically starts between E8-E9. Beating was eliminated by Ca channel blocker nifedipine and the I(f) blocker ZD7288, unaffected by tetrodotoxin and only mildly depressed by disabling sarcoplasmic (SR) and endoplasmic (ER) reticulum Ca cycling. From E8.5 to E10, conduction velocity increased from 0.2-1 mm/s to >5 mm/s in first ventricular and then atrial tissue, while remaining slow in other areas. Arrhythmias included atrioventricular reentry induced by adenosine. In summary, at the onset of beating, I(f)-dependent pacemaking drives both AP propagation and Ca(i) transient generation through activation of voltage-dependent Ca channels. Na channels and intracellular Ca cycling have minor roles.
Chen
Fuhua
F
UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California-Los Angeles, 675 Charles Young Drive South, Los Angeles, CA 90095, USA.
De Diego
Carlos
C
Chang
Marvin G
MG
McHarg
Jennifer L
JL
John
Scott
S
Klitzner
Thomas S
TS
Weiss
James N
JN
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D054537:Atrioventricular Block / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy
D002121:Calcium Channel Blockers; D009543:Nifedipine; D002118:Calcium