U.Va. researchers discover mechanism for the regulation of low-voltage-activated calcium channels

Researchers at the University of Virginia Health System have defined a molecular mechanism by which the activity of low-voltage-activated calcium channels can be decreased. Low-voltage-activated, T-type calcium channels are found in many types of tissue and alterations in their activity can contribute to several pathological conditions, including congestive heart failure, hypertension, cardiac arrhythmias, epilepsy and neuropathic pain. The findings will be published in the July 10 edition of Nature. The team led by Paula Q. Barrett, professor of pharmacology and principle investigator of the study, found that G-protein beta gamma subunits, a class of cell membrane proteins that mediate the actions of hormones within the cell, markedly decrease the flow of calcium through these channels into the cell interior. Because elevation of calcium within cells stimulates cellular activity, regulation of calcium entry is an important way by which the function of cells can be controlled. The research uncovered that only one member of a large family of G-protein subunits binds directly to the calcium channel protein to inhibit channel activity.

“These studies identify the T-type calcium channel as a new target for G-protein beta gamma subunits,” Barrett said. “The extraordinary specificity of the interaction between these regulatory molecules could be operative in many types of cells and provides exciting insight into the highly selective ways in which cells work. Knowledge of these interactions will lead to the development of new and more specific drugs in the future.”

Joshua T. Wolfe, a graduate student whose work is supported by the American Heart Association, conducted much of the work for this research. Support for the research also came from the National Institutes of Health and the University of Virginia Cardiovascular Research Center.