March 9, 2011
Researchers In France And Austria Find Novel Role For Calcium Channels In Pacemaker Cell Function
Pacemaker cells in the sinoatrial node control heart rate, but what controls the ticking of these pacemaker cells? New research by Angelo Torrente and his colleagues of the M.E. Mangoni group's, reveals, for the first time, a critical functional interaction between Cav1.3 calcium ion (Ca2+) channels and ryanodine-receptor (RyR) mediated Ca2+ signaling.
The study also sheds light on a long-standing debate regarding the relative contributions of the 'funny current' generated by ion channels and the RyR dependent spontaneous diastolic Ca2+ release theory in determining heart rate.
Defects in calcium channels controlling heart muscle function are known to cause heart failure, and this study reveals that Cav1.3 mutant mice also suffer from bradycardia and other cardiac arrhythmias.
"Our results clarify the role of Cav1.3 channels in pacemaker generation, and are a step towards using it as a target for drug therapy to treat heart dysfunction related to the sinoatrial node", says A. Torrente of CNRS in Montpellier, France, who was the lead author on the study.
Not only Cav1.3 channels are critical to the heart pacemaker cell function, they appear to be important to several other cellular mechanisms as well. In both humans and mice, Cav1.3 mutations have been linked to sinoatrial node dysfunction and deafness (or SANDD) syndrome. Cav1.3 channels are believed to play a role in pancreatic Ã²-cell stimulation, and they may also serve as pacemaker channels in the central nervous system, playing a pathophysiological role in Parkinson's disease.
"A better understanding of these channels in SAN could help us to comprehend the mechanism of calcium release in many other tissues and disease conditions as well", says Torrente.
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