Crosstalk between ion channels leads to new therapeutic trategy

By ANI
Monday, September 20, 2010

WASHINGTON - Scientists have found a new target for fighting cystic fibrosis (CF) that could compensate for the lack of a functioning ion channel in affected CF-related cells.

The lab of Kevin Foskett at the University of Pennsylvania School of Medicine explored the role of CFTR, the chloride ion channel mutated in CF patients, in fluid secretion by mucous gland cells.

They used a recently developed transgenic pig model, in which the CFTR gene has been knocked out.

The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. The flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucous.

CF researchers had been held back because existing animal models did not fully mimic the problems seen in people with CF.

In people, faulty mucous glands may contribute to airway dehydration and the problems associated with CF.

“We discovered, first, that the ion transport and signal transduction mechanisms in the pig cells appear to be precisely the same as those used in human cells, indicating that the pig is an excellent model for studies of human lung function and a valuable tool for elucidating pathology of lung disease in CF,” noted Foskett.

The team also discovered that fluid secretion by the mucous cells-in response to neurotransmitters-required CFTR. This secretion was absent in the pigs lacking CFTR.

However, the same cells that lacked the CFTR chloride ion channel, mimicking the condition in human CF, expressed another, different chloride ion channel that could be activated by elevating intracellular calcium by the same neurotransmitters.

The presence of both channels in the same mucous cells suggested that the calcium-activated chloride channel could be targeted therapeutically to compensate for lack of CFTR functioning channels in CF-harmed cells.

“This crosstalk between the signalling pathways that activate the two different chloride ion channels now gives us a completely new therapeutic strategy to think about,” said Foskett.

Their findings appeared in the Journal of Clinical Investigation. (ANI)

Filed under: Science and Technology

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