University of Pennsylvania Biologists Reveal Neuronal Channel That Regulates Breathing

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Media Contact:Jordan Reese | jreese@pobox.upenn.edu | 215-573-6604May 16, 2007

PHILADELPHIA -- Biologists at the University of Pennsylvania have found a link between a recently discovered protein in the brain and the nervous system's duty to regulate respiration.

For decades, researchers have investigated how the brain "unconsciously" controls breathing, a chemical and electrical process considered automatic in the mammalian world.  

The Penn study demonstrated that NALCN, a substantially uncharacterized member of the sodium/calcium ion channel gene family, plays a key role in respiration by forming a channel in the brain cells that allows a constant, regulated "leak" of the positively charged sodium ions into the neurons.  It may be this continual transference of sodium that triggers regular excitement of the brain stem, the portion of the brain associated with a variety of functions including motor control, and respiration.

All living beings rely upon the traffic of charged chemicals (normally sodium, potassium or calcium) in the brain to fire neurons, leading to the complex processes that sustain life, among them respiration.

Testing their findings, Penn researchers genetically mutated mice in the embryonic stem cell phase to prevent their production of NALCN.  The resulting specimens experienced severely disrupted respiratory rhythm and died within 24 hours of birth.  In addition, brainstem-spinal cord recordings revealed reduced brain activity.  

The NALCN channel appears to be a regulating gateway that controls the chemical energy required to fire neurons and thus regulate the breathing required to sustain life.

"Surprisingly, how the neurons generate and control breathing rhythm is poorly understood," said Dejian Ren, assistant professor of biology at Penn's School of Arts and Sciences.  "The discovery of this important ion channel may open the door to a further understanding at the molecular level."

The findings are relevant to more than just those suffering from breathing disorders, as the NALCN protein is also found in other brain regions whose irregularities affect those suffering from epilepsy, seizures, depression, bi-polar disorders and schizophrenia.

The study was conducted by Dejian Ren, Boxun Lu, Yanhua Su, Sudipto Das, Jin Liu and Jongsheng Xia of Penn's Department of Biology and was published in the journal Cell.

The research was supported in part by the American Heart Association and the University of Pennsylvania Research Foundation.

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