Emerging novel molecular targets in anti-arrhythmic therapy 

 Basic Science Track

The regulatory intracellular calcium handling system as an emerging target for anti-arrhythmic drug development.

A micro-array expression profile in a dog model of rapid pacing-induced heart failure is feasible and allows to correlate the temporal gene expression with the evolving electrophysiological derangements (prolongation of action potential duration and slowing of conduction velocity).

Heart failure is associated with abnormal SR calcium release, hyperphosphorylation of ryanodine receptors, activation of the Na + / Ca 2+ exchanger in the reverse mode, and overexpression and function of Ca MKII. Drugs that modulate the function of this calcium handling protein system may have the potential to exert antiarrhythmic effects. However, like CaMK (see figure), most of the calcium handling modulators exert their effects at various intracellular sites and cellular structures. Thus a better knowledge of these interactions is needed to develop drugs with a resultant net beneficial action. Moreover, most of our knowledge on the relationship between intracellular calcium and arrhythmogenesis linked to afterdepolarizations is based on experimental models of ventricular arrhythmias.