Transplantation of autologous skeletal myoblasts (SMBs) is a potential therapeutic approach for
myocardial infarction. However, their clinical efficacy and safety is still controversial. Electrical coupling through gap junction between SMBs and host myocardium is essential for synchronized contraction and electrical stability. Here, we investigated the effect of heart beat-simulating environment, oscillating pressure, on the expression of
connexin43 in two types of SMBs from rat and mouse. We found that
connexin43 is markedly decreased under
ischemia-mimicking conditions such as serum
starvation and
hypoxia (1% O(2)) in rat primary cultured SMBs and mouse C2C12 SMB cell line. Interestingly, the decrease of
connexin43 expression under serum
starvation was attenuated by oscillating pressure. Oscillating pressure treatment increased the expression of
connexin43 twofold through
AP-1 stimulation, which was blocked by
PD98059, ERK inhibitor. In coculture of cardiomyocytes and C2C12, pressure-treated C2C12 and cardiomyocytes were able to form functional gap junction, which was demonstrated by both
calcein-AM dye transfer assay and measurement of simultaneous contraction. In rat
myocardial infarction model,
transplantation of SMBs pretreated with oscillating pressure resulted in lesser ventricular dilatation and better systolic function than
transplantation of untreated SMBs and control group. These results suggested that application of oscillating pressure on SMBs before
transplantation may be useful to promote therapeutic efficacy for
myocardial infarction by enhancing gap junction formation between transplanted and host cells.