Investigation of the relation between electrical remodeling of cardiac hypertrophy and Rho/ROCK pathway

Objective: Various cardiovascular diseases like myocardial infarction, heart failure and cardiac hypertrophy are associated with the RhoA/Rho kinase (ROCK) signaling pathway. In this respect, we examined the effect of ROCK inhibition on potassium K+ currents and AP in pressure overload (PO) cardiac hypertrophy model. Method: PO model is created by aortic constriction (TAC) of rat's heart. SHAM animals underwent surgery without banding. All data taken from three groups SHAM, TAC and 10 weeks fasudil (5mg/kg) administered TAC (T+F) group using electrophysiological and protein expression analysis techniques. Data were recorded by applying voltage steps from holding potential of -70 mV in 10 mV increments, between -120 to 10 mV for inward rectifier K+ currents (IK1) and -50 to 70 mV for transient outward K+ currents (Ito). Results: There was significant prolongation Aps of TAC myocytes recorded at 1 Hz which was restored in T+F group. Density of both potassium currents decreased significantly with cardiac hypertrophy but fasudil reversed currents to control level. According to protein analysis, Kv4.2 expression was higher in TAC group and it didn't reverse in T+F group. Despite RhoA expression increased significantly, ROCK1&2 and Kir2.1 decreased in TAC group. Fasudil treatment restored the expression level of these proteins after 10 weeks decreased after 10 weeks. Conclusion: In summary, fasudil improves not only IK1 and Ito currents but also protein expressions of RhoA/ROCK pathway elements and shortens AP duration. As a result, RhoA/ROCK pathway may play role in electrical remodeling of heart and thus inhibition of this pathway may be used as potential therapeutic purposes. Key words: Rho, ROCK, fasudil, K+ currents, action potential