Calcium Channel Defect Causes Deafness, Irregular Heartbeat

Ten years ago, scientists seeking to understand how a certain type of cell feature called an L-type calcium channel worked created a knockout mouse missing both copies of the CACNA1D gene. The CACNA1D gene makes a protein that lets calcium flow into a cell, transmitting important instructions from other cells. The knockout mice lived a normal life span, but their hearts beat slowly and arrhythmically. They were also completely deaf. On March 9, 2011, at the 55th Annual Biophysical Society Meeting in Baltimore, an international team lead by Dr. Hanno Bolz of the University of Cologne in Germany reported identification of a mutation on the CACNA1D gene affecting two families in Pakistan. The altered gene adds one extra amino acid to the middle of the protein, which is more than 2,000 amino acids in length. The result is that family members with two copies of the mutated gene are not only deaf, but also have an irregular heartbeat. "Their heart beats slowly, dropping below 30 beats a minute during sleep," said Dr. Joerg Striessnig, professor at the University of Innsbruck in Austria and one of the study’s senior authors. The researchers analyzed the family's mutation and determined that it does not destroy the protein, said Dr. Striessnig. "Normally, part of the protein acts like a hinge to open the calcium channel once the cell gets stimulated. The mutated protein still sits in the cell's surface membrane where it should be, but the hinge does not open the channel," he said. "It's not only interesting for medicine but also for understanding how these channels work as molecular machines." [Press release]
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