Elimination of Cav3.1 expression in mice led to increased ventricular tachycardia inducibility post-myocardial infarction (82% vs 30%; P<0.05) compared to wild-type controls.
Does genetic elimination of Cav3.1 or Cav3.2 T-type calcium channel subunits improve cardiac function and reduce arrhythmia vulnerability post-myocardial infarction in mice?
Contrary to previous pharmacological studies, genetic elimination of the Cav3.1 T-type calcium channel subunit impairs cardiac function and increases arrhythmia vulnerability post-myocardial infarction in mice.
Absolute Event Rate: 82% vs 30%
p-value: p=< 0.05
AIMS: Previous studies suggested that T-type Ca(2+)-current (I(CaT))-blockers improve cardiac remodelling, but all available I(CaT)-blockers have non-specific actions on other currents and/or functions. To clarify the role of I(CaT) in cardiac remodelling, we studied mice with either of the principal cardiac I(CaT)-subunits (Cav3.1 or Cav3.2) knocked out. METHODS AND RESULTS: Adult male Cav3.1- or Cav3.2-knockout (Cav3.1(-/-), Cav3.2(-/-)) mice and respective wild-type (WT) littermate controls were subjected to left anterior descending coronary artery ligation to create myocardial infarction (MI). Echocardiography and programmed electrical stimulation were performed at baseline and 4 weeks post-MI. At baseline, Cav3.1(-/-) mice had slowed heart rates and longer PR intervals vs. WT, but no other electrophysiological and no haemodynamic differences. Cav3.2(-/-) showed no differences vs. WT. Contractile indices (left ventricular fractional shortening and ejection fraction) decreased more post-MI in Cav3.1(-/-) mice than in Cav3.1(+/+) (e.g. by 34 and 29% for WT; 50 and 45% for Cav3.1(-/-), respectively; P < 0.05 for each). Cav3.1(-/-) mice had increased ventricular tachycardia (VT) inducibility post-MI (9 of 11, 82%) vs. WT (3 of 10, 30%; P < 0.05). Cav3.2(-/-) mice were not different in cardiac function or VT inducibility vs. WT. Quantitative polymerase chain reaction showed that Cav3.1 is the major I(CaT)-subunit and that no compensatory Cav3.2 up-regulation occurs in Cav3.1(-/-) mice. Cav3.1(-/-) and Cav3.2(-/-) mice had no mRNA expression for the knocked-out gene, at baseline or post-MI. CONCLUSION: Our findings suggest that, contrary to suggestions from previous studies with (imperfectly selective) pharmacological agents having T-type Ca(2+)-channel-blocking actions, elimination of Cav3.1 expression leads to impaired cardiac function and enhanced arrhythmia vulnerability post-MI, whereas Cav3.2 elimination has no effect.
Quang et al. (Fri,) conducted a other in Myocardial infarction. Cav3.1 knockout vs. Wild-type (WT) littermate controls was evaluated on Ventricular tachycardia (VT) inducibility post-MI (p=< 0.05). Elimination of Cav3.1 expression in mice led to increased ventricular tachycardia inducibility post-myocardial infarction (82% vs 30%; P<0.05) compared to wild-type controls.