Calcium-dependent potassium channels as target to increase drug delivery to brain tumors

LOS ANGELES (May 22, 2002) In a study conducted in rats, researchers at Cedars-Sinais Maxine Dunitz Neurosurgical Institute modulated the calcium-dependent potassium channels of blood vessel cells to increase permeability of the blood-brain tumor barrier (BTB). As a result, they were able to selectively deliver drugs directly to the area of brain tumors without increasing delivery to normal brain tissue.

Results of the study appear as the cover article of the June issue of the Journal of Pharmacology and Experimental Therapeutics. The findings represent what may be a major step toward providing significantly more effective drug therapy for patients suffering from brain tumors.

The blood-brain tumor barrier is a mechanism that naturally occurs within brain tumor capillaries, the tiny blood vessels at the ends of small arteries that feed a tumor. The BTB functions as a tumors defense mechanism, significantly blocking the amount of cancer-killing medications that reach the tumor.

The key to the blood-brain tumor barrier and the researchers ability to manipulate it is the activity that takes place within the cells of tumor capillaries at the calcium-dependent potassium channels.

Many functions of cells depend on positive- and negative-charged chemicals, or ions, flowing into and out of the cells through membranes. Ions enter and exit through protein structures called channels. Specific channels permit passage of specific ions, and gates open and close to regulate the flow. While some gates are controlled by voltage changes, others are activated by the presence of a secondary chemical, in this case, calcium.

Previous studies have shown that calcium-dependent potassium channels in cerebral blood vessels regulate vessel tone, affecting dilation and constriction. Another important function performed by calcium-dependent potassium channels is preventing toxins in the bloodstream from passing through the cells and reaching those of t

Contact: Sandra Van
Cedars-Sinai Medical Center

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