Abstract 216: Pressure-Overload-Induced Cardiac Hypertrophy is Impaired in CaV3.2 T-Type Ca2+ Channel-Deficient Mice
Background: Voltage-gated T-type Ca2+ current is temporarily recorded in cardiac myocytes during fetal and neonatal period in some rodents and reappears in hypertrophied or failing hearts, implying that T-type Ca2+ channel (T-channel) might play a role in the pathogenesis of heart diseases. There are two types of T-channel expressed in the heart, namely CaV3.1 and CaV3.2.
Methods and Results: To assess the hypothesis that the re-expressed T-channels are involved in the cardiac remodeling during the pathogenesis of hypertrophy, CaV3.2 T-type Ca2+ channel-deficient mice (CaV3.2−/ −) were subjected to transverse aortic constriction (TAC) and thereafter the progression of cardiac hypertrophy and function was examined. At the basal level, there is no significant difference between wild type (WT) and CaV3.2−/ − in the percentage of fractional shortening and the left ventricular mass/body weight (LVM/BW, mg/g) ratio as determined by echocardiography. After 2 weeks of TAC, WT showed a significant increase of LVM/BW ratio (3.96 ± 0.13 (sham-operated, n=6) and 6.01 ± 0.25 (TAC, n=11), p< 0.001). In contrast, the pressure-overload-induced hypertrophy was blunted in CaV3.2−/ −, the LVM/BW ratios were 4.24 ± 0.13 (sham-operated, n=7) and 4.11 ± 0.22 (TAC, n=12), p=0.3. G protein (Gq/11)-coupled receptor mediated pathway has been shown to be essential for cardiac hypertrophy induced by pressure overload. To examine whether direct stimulation of Gq-coupled receptors could induce cardiac hypertrophy in CaV3.2−/ −, angiotensin II (AngII, 1.3mg/kg/d) were continuously infused via osmotic minipump for 7 days. Conversely, the AngII-induced cardiac hypertrophy was blunted in the CaV3.2−/ −, the LVM/BW ratios were 3.64 ±0.04, n=4 and 5.24 ± 0.12, n=4 (p<0.01) in CaV3.2−/ − and WT, respectively.
Conclusion: These findings suggest that CaV3.2 is pivotal for the activation of pathological hypertrophy in mice and establish genetic evidence of the necessity for CaV3.2 in triggering cardiac hypertrophy in response to TAC or angiotensin II.