Table 1.

The role of ECC proteins during embryonic heart development

Protein (gene)	Cardiac phenotype
NCX1 (Slc8a1)	Lethality E9 to E10; thin myocardium with reduced cardiomyocytes; no heartbeat observed (Wakimoto et al. 2000)
	Lethality E9.0 to E9.5; underdeveloped heart with dilated pericardium; contractile although significantly slower than wild-type (WT) littermates; mutant and WT hearts indistinguishable at E8.5 (Cho et al. 2000)
	Lethality E11.5 to E13.5; lack of a spontaneous beating heart and organized myofibrils (Koushik et al. 2001)
Cav1.2 (Cacna1c)	Lethality prior to E14.5; normal development until E12.5, contractile rate the same as WT littermates (Seisenberger et al. 2000)
Cav1.3 (Cacna1d)	Viable embryos; pronounced bradycardia and arrhythmias at rest in the adult; altered sinoatrial pacemaker activity (Platzer et al. 2000)
RyR2 (Ryr2)	Lethality E10.5 to E11.5; rhythmic contractions at E9.5, although irregularly arranged myocardium; no heartbeat at E10.5, anatomically similar to E9.5 (Takeshima et al. 1998)
SERCA2a (Atp2a2)	No mutant embryos detected with germline deletion (Periasamy et al. 1999); conditional myocardial deletion led to lethality at E11.5; circulation and heartbeat observed until E10.5 (Andersson et al. 2009)
Nav1.5 (Scn5a)	Lethality E10.5 to E11.5; some uncoordinated beating at E10.5, however, none observed at E11.5; reduced ventricular chamber size, trabeculation, and cardiomyocytes (Papadatos et al. 2002)
HCN4 (Hcn4)	Spontaneous beating E8.5–E10.5 although reduced rate of contraction; lethal between E9.5 and 11.5 (Stieber et al. 2003)
cTnT (Tnnt2)	Lack of heartbeat while Ca2+ transients still detected; no phenotypic differences until E8.75 leading to looping defects, sarcomere disassembly, and dilated hearts; lethality between E10.5 and 11.5 (Nishii et al. 2008)

Summary of studies in which proteins required for excitation–contraction coupling (ECC) cardiac physiology and Ca²⁺ handling have been deleted in mice. All deletions are germline unless otherwise stated.