Late Sodium Current

The Science of the Late Sodium Current

Scientists at CV Therapeutics are engaged in a program to identify novel, orally bioavailable blockers of the late sodium current that may be effective in the treatment of some cardiovascular diseases. The goals of our late sodium current program are to further characterize potential therapeutic areas and to discover new, proprietary products.

Every heartbeat is coordinated by electrical currents generated by the movement of charged ions in and out of cardiac muscle cells (cardiomyocytes) through channels. Several ions, including sodium and calcium, are involved in the normal contraction and relaxation cycle of the heart.

A defect in sodium channels that allows a persistent leak of sodium may lead to a potentially harmful excess of sodium and calcium ions inside cardiomyocytes. The current that is associated with the leak of sodium through channels that fail to close properly is called the late sodium current. Scientists have discovered the potential importance of this defect as a research target for the possible treatment of a variety of cardiovascular conditions.

As shown in preclinical studies, in the normal heart, a rapid influx of positively charged sodium ions into the cell through the sodium channel creates an electrical excitation that starts the contraction process. Normally, the sodium channel opens and shuts very quickly. This causes the rapid depolarization of cardiac cells seen on a typical electrocardiogram (ECG, EKG). However, during both ischemia and heart failure but not under other conditions or in the normal heart, some sodium channels may not close properly and may lead to sodium overload and subsequent calcium overload in the cardiomyocyte. These conditions prevent the heart from achieving complete relaxation during diastole and can increase energy demand. Diastolic tension may also compress microvascular blood flow and reduce oxygen supply to the cardiomyocytes, resulting in worsening of myocardial function. View an image of the ischemic cycle.