Grant: Operating Grant

Sodium channels are pores present at the surface of every cardiac cells, they allow exclusively sodium ions to enter the cell, they are very crucial for initiating heart beats and its regular rhythmicity. These sodium selective pores are blocked by antiarrhythmics, drugs used to treat heart rhythm disturbances especially when heart rhythm is out of control. Indeed, sodium channel blockade has been the foundation of the therapy of cardiac arrhythmias in several cardiovascular diseases. Despite the addition of new drugs to the older drug arsenal, they failed to completely suppress arrythmogenesis and the presence of adverse side-effects of the drugs still limit their therapeutic usefulness. The molecular components that form the intracellular pore, where these drugs bind are not well elucidated. Using molecular biology techniques we will introduce amino-acid replacement of key residues and test their role in forming the pore. To achieve this goal it is necessary to alter the structure of cardiac sodium channels and evaluate the effects of those alterations on function. Cardiac sodium channels will be expressed in cells; this is an advantageous system to perform experiments which help us to better understand the structure and function of the human cardiac sodium channels. This will provide us with some extremely important information on the structure of the pore and finding the means of treating heart rhythm disorders. Finally, study of cardiac sodium channel pore, hopefully, will lay the groundwork for the design of new drugs targeted more specifically at maintaining cardiac sodium channels in nonconducting state.