Oxygen sensitivity in the sheep adrenal medulla: role of SK channels.
The hypoxia-evoked secretion of catecholamines from the noninnervated fetal adrenal gland is essential for surviving intrauterine hypoxemia. The ion channels responsible for the initial depolarization that leads to catecholamine secretion have not been identified. Patch-clamp studies of adrenal chromaffin cells isolated from fetal and adult sheep revealed the presence of a Ca(2+)-dependent K(+) current that was reduced by hypoxia. Apamin, a blocker of small-conductance K(+) (SK) channels, reduced the Ca(2+)-dependent K(+) current, and the sensitivity of the channels to apamin indicated that the channels involved were of the SK2 subtype. In the presence of apamin, the hypoxia-evoked change in K(+) currents was largely eliminated. Both hypoxia and apamin blocked a K(+) current responsible for maintaining the resting potential of the cell, and the depolarization resulting from both led to an influx of Ca(2+). Simultaneous application of hypoxia and apamin did not potentiate the increase in cytosolic Ca(2+) concentration beyond that seen with either agent alone. Similar results were seen with curare, another blocker of SK channels. These results indicate that closure of SK2 channels would be the initiating event in the hypoxia-evoked catecholamine secretion in the adrenal medulla.
Keating
D J
DJ
Department of Physiology, University of Adelaide, Adelaide 5005, Australia.
Rychkov
G Y
GY
Roberts
M L
ML
D000313:Adrenal Medulla / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D000860:Hypoxia / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011247:Pregnancy; D012756:Sheep; D051640:Small-Conductance Calcium-Activated Potassium Channels
D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D010100:Oxygen; D002118:Calcium