Oxygen sensing in the sheep adrenal medulla.

Abstract

In the fetus, prior to the development of adrenal innervation, hypoxia acts directly on the adrenal medulla to stimulate catecholamine secretion which triggers a set of physiological responses that are imperative for intrauterine survival. This direct response to hypoxia is suppressed upon development of the splanchnic innervation, but reappears if the gland is denervated. In the glomus cells of the carotid body, hypoxia evokes the release of dopamine by closing Ko2 channels, leading to membrane depolarisation, Ca2+ entry through voltage-gated Ca2+ channels and subsequent catecholamine secretion. Ko2 channels also exist in the adrenal medulla, but it is unknown whether these channels play a role in initiating the response by depolarising the cell or what intracellular mechanisms enable O2 levels to control Ko2 channel function. The means by which adrenal gland innervation is able to suppress the direct hypoxic response also remains unclear, though it is likely due to the actions of a substance released from the nerve terminals, as the direct hypoxic response returns rapidly upon denervation of the gland. The aims of this study therefore, were: 1) to identify the channel(s) which cause the responses to hypoxia observed in the adrenal medulla. 2) investigate the different types of Ca2+ channels which are present, their contribution to Ca2+ entry and whether any particular Ca2+ channels modulate K+ channels in these cells. 3) find the intracellular pathways which transmit the decrease in extracellular O2 levels to the membrane bound ion channels. 4) find whether the actions of opioid peptides, which are released from nerve terminals innervating the adrenal medulla, account for the suppression of the direct response upon innervation by altering either K+ or Ca2+ channel function.