Caveolin-3 is a muscle-specific
protein on the membrane of myocytes correlated with a variety of
cardiovascular diseases. It is now clear that the
caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding
caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of
creatine kinase in asymptomatic humans to
cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in
long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (IK1) and gain of the late
sodium current (INa-L). The functional significance of the
caveolin-3 has proved that
caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias.
Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca2+ waves, thus leading to the abnormal
L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated
cyclic nucleotide channel 4 current (IHCN4) activation curve and a significant decrease in IHCN4 whole-cell current density. Recent evidence indicates that
caveolin-3 plays a significant role in adipose tissue and is related to
obesity development. The role of
caveolin-3 in
glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of
caveolin-3 in
arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing
arrhythmia.