Question: 

Cardiovascular diseases account for 16.7 million deaths per year, all over the world. The main cause of these diseases is cardiac hypertrophy. Although hypertrophy is primarily a compensatory response, sustained growth may gradually lead to structural and electrophysiological remodeling and finally to dilated heart chambers, arrhythmia and even sudden death. Therefore, procedures that limit such growth responses should be studied in order to develop therapeutic strategies. Among heterotrimeric G-proteins, the Ga_q/a₁₁ signaling cascade is crucial in the induction of pathological cardiac hypertrophy.

Methods: 

Here we used a Ga₁₁ knock out (KO) and Ga_q/a₁₁ double knock out (DKO) mouse model to study the mechanisms of hypertrophy. In order to induce hypertrophy, we implanted osmotic mini-pumps with aldosterone inducing hyperaldosteronism (7.2mg/day). Into the same genotypes, we implanted dummy pumps as control. Electrophysiological parameters such as resting membrane potential (V_R), action potential duration (APD) and 2 types of potassium currents (I_to and I_ss) were investigated in the whole cell configuration of the patch clamp technique.

Results: 

Membrane capacitance and V_R remained unchanged in both Ga₁₁KO and Ga_q/a₁₁DKO but APD30 showed a significant shortening in Ga_q/a₁₁DKO after aldosterone infusion. I_to increased significantly in Ga_q/a₁₁DKO but I_ss remained unchanged in both groups.

Conclusion: 

Electrophysiological remodeling associated with hypertrophy such as APD prolongation or I_to decrease were both absent in transgenic mice lacking either Ga₁₁ or Ga_q/a₁₁ supporting the seminal importance of the signaling cascade in the development of aldosterone dependent hypertrophic remodeling.