Increased catecholamine secretion from single adrenal chromaffin cells in DOCA-salt hypertension is associated with potassium channel dysfunction.
The mechanism of catecholamine release from single adrenal chromaffin cells isolated from normotensive and DOCA-salt hypertensive rats was investigated. These cells were used as a model for sympathetic nerves to better understand how exocytotic release of catecholamines is altered in this model of hypertension. Catecholamine secretion was evoked by local application of acetylcholine (1 mM) or high K+ (70 mM), and continuous amperometry was used to monitor catecholamine secretion as an oxidative current. The total number of catecholamine molecules secreted from a vesicle, the total number of vesicles fusing and secreting, and the duration of secretion in response to a stimulus were all significantly greater for chromaffin cells from hypertensive rats as compared to normotensive controls. The greater catecholamine secretion from DOCA-salt cells results, at least in part, from functionally impaired large conductance, Ca2+-activated (BK) and ATP-sensitive K+ channels. This work reveals that there is altered vesicular release of catecholamines from these cells (and possibly from perivascular sympathetic nerves) and this may contribute to increased vasomotor tone in DOCA-salt hypertension.
Department of Chemistry, ‡Department of Pharmacology and Toxicology, and §The Neuroscience Program, Michigan State University , East Lansing, Michigan 48824, United States.
Matthew J
MJ
Fhaner
James J
JJ
Galligan
Greg M
GM
Swain
D000255:Adenosine Triphosphate / Q000502:physiology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000172:deficiency* / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D003900:Desoxycorticosterone; D000255:Adenosine Triphosphate