To obtain functional evidence that ICa,T is involved in the pathogenesis of cardiac hypertrophy and heart failure. We unexpectedly identified ICa(TTX) rather than ICa,T, therefore, we adjusted our aim to encompass these findings.
Methods and Results:
We investigated (1) Cav3.1 (α1G) transgenic (Tg) mice compared with nontransgenic (tTA-Ntg); (2) Cav3.1-deficient mice (Cav3.1−/−) compared with wild type (Wt) after chemically and surgically induced cardiac remodeling; and (3) spontaneous hypertensive rats and thoracic aortic constriction (TAC) rats. Whole-cell patch-clamp technique was used to measure ICa in ventricular myocytes. Cav3.1-Tg expressed ICa,T (−18.35 ± 1.02 pA/pF at −40 mV) without signs of compromised cardiac function. While we failed to detect ICa,T after hypertrophic stimuli, instead we demonstrated that both Wt and Cav3.1−/− mouse exhibit ICa(TTX). Using TAC rats, only 2 of 24 VMs showed ICa,T under our experimental conditions. Without TTX, ICa(TTX) occurred in VMs from Wt, spontaneous hypertensive rats, and TAC rats also.
These findings demonstrate for the first time that mouse VMs express ICa(TTX). We suggest that future studies should take into consideration the measuring conditions when interpreting ICa,T reappearance in ventricular myocytes in response to hypertrophic stress. Contamination with ICa(TTX) could possibly confuse the relevance of the data.