Regulation of Cardiac Ion Channel Function: The Na+ channel (SCN5A, LQT3) and two K+ channels, HERG (LQT2) and KVLQT1 (LQT1) are linked to the inherited Long QT Syndrome and are responsible for cardiac action potential initiation and termination for each heart beat. Appropriate activation of these channels terminates each action potential allowing the next heart beat to occur in a normal fashion. Macromolecular signaling complexes involving channels may serve multiple functions including assembly, trafficking, targeting, and recycling of the channel proteins. Dynamic, beat-to-beat regulation of cardiac ion channels is likely to be precisely controlled given that both acquired and inherited ventricular arrhythmias are usually episodic and precipitated by some stimulus or stress. Moreover, such regulation may underlie the responses to cardiovascular challenges and stresses that eventually lead to maladaptive "electrical remodeling" with cardiac arrhythmias.
The McDonald laboratory employs a multifaceted approach to understand how these channels are regulated by accessory subunits, protein kinases, and adaptor proteins. Specific projects focus on:
Potassium Channels of Protozoan Parasites: All living cells express membrane ion channels that are evolutionarily conserved. These channels provide selective permeability characteristics of cell membranes and are essential for normal cell function and viability. The McDonald laboratory has identified and cloned a series of related K+ channel genes from intracellular parasite genomes (Malaria, Leishmania, Toxoplasma) and mycobacterium. They are now investigating these channel gene products for their roles as determinants of cell function, viability, infectivity and virulence. The long term goal of this research is to identify essential functional proteins that may serve as pharmacological or immunological targets.
More Information About Dr. Thomas McDonald
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room G42
Bronx, NY 10461
CNN interviews Drs. Thomas McDonald and Robert Marion about the Montefiore-Einstein Center for Cardiogenetics, which studies sudden death in infants (SIDS) and adults (SUDS).