Expression and function of mitochondrial inhibitor factor-1 and TASK channels in adrenal cells.

Adrenal medullary chromaffin (AMC) cells in the perinatal period and carotid body glomus cells after birth respond to hypoxia with catecholamine secretion. The hypoxia detection mechanism in such O 2 -sensitive cells is still not well defined. One hypothesis is that a decrease in cellular ATP may be involved in the hypoxia detection. This idea is based on ATP dependence of TASK channel activity that regulates the resting membrane potential and is suppressed by hypoxia in glomus cells. Mitochondrial ATPase inhibitor factor-1 (IF 1), a physiological regulator of ATP synthase, helps prevent ATP hydrolysis under hypoxic conditions. In cells where IF 1 expression is high, exposure to hypoxia is expected to have no effect on TASK channel activity. This possibility was electrophysiologically and immunocytochemically explored. Single channel recordings revealed that 36-pS TASK3-like channels contribute to the resting membrane potential in young rat adrenal cortical (AC) cells. TASK3-like channel activity in a cell-attached patch was not affected by bath application of mitochondrial inhibitors. Consistent with this finding, IF 1 -like immunoreactive material was well expressed in rat AC cells. In further support of our hypothesis, IF 1 -like immunoreactive material was well expressed in adult rat AMC cells that are known to be hypoxia-insensitive and minimally expressed in newborn AMC cells that are hypoxia-sensitive. These results provide evidence for the functional relevance of IF 1 expression in excitability in O 2 -sensitive cells in response to mitochondrial inhibition. • IF 1 was well expressed in adult rat adrenal medullary chromaffin (AMC) cells. • IF 1 expression was minimal in newborn AMC cells. • IF 1 was well expressed in both newborn and adult adrenal cortical (AC) cells. • 36-pS TASK3-like channels were active at rest in young AC cells. • Mitochondrial inhibitors did not affect TASK3-like channels in young AC cells. [ABSTRACT FROM AUTHOR]