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Richard Veenstra, PhD

Veenstra Lab

This laboratory is interested in how cells communicate electrically and chemically via gap junctions to promote synchronized function and tissue homeostasis. The name "gap junction" refers to the "tunnel" that directly connects the cytoplasm of adjacent cells by a water-filled pore formed by proteins called connexins.

Gap junctions are vital to all tissue function as evidenced by the association of mutations in half of the twenty known connexin proteins with human diseases such as deafness, keratitis, cataracts, and neuropathies. Electrical signal trandsduction is especially important in the heart since the 1/10th of a volt signal that begins with the "pacemaker" has to conduct through the millions of cardiomyocytes within a quarter of a second with every heartbeat. Once thought to be always open, gap junctions are now known to be regulated by many biological factors including extracellular and intracellular calcium ions, pH, protein phosphorylation, and now protein acetylation.

Today, there is no clinically approved pharmacological drug that directly targets gap junctions to treat human ailments. This laboratory is studying how the connexin proteins form the pore of the gap junction channel, how they are regulated by calcium, calmodulin, and new therapeutic drugs, and why dysregulation or loss-of-function connexin mutations cause cardiac arrhythmias or other human diseases. One of the scientific techniques we use to study gap junctions is the two cell patch clamp technique shown in this picture, where we move two microscopic glass electrodes onto two coupled cells to enable us to directly measure the electric current flowing through the gap junctions linking those two cells. We use cell lines to express mutant connexins and native heart cells, cardiomyocytes, to study the effects of mutations and regulatory factors (calcium) or drugs on cardiac, and other, gap junctions.

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