| Autor: |
Enyeart JJ; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio., Enyeart JA; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio. |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2021 Jul 01; Vol. 321 (1), pp. C158-C175. Date of Electronic Publication: 2021 May 26. |
| DOI: |
10.1152/ajpcell.00118.2021 |
| Abstrakt: |
In whole cell patch clamp recordings, it was discovered that normal human adrenal zona glomerulosa (AZG) cells express members of the three major families of K + channels. Among these are a two-pore (K2P) leak-type and a G protein-coupled, inwardly rectifying (GIRK) channel, both inhibited by peptide hormones that stimulate aldosterone secretion. The K2P current displayed properties identifying it as TREK-1 (KCNK2). This outwardly rectifying current was activated by arachidonic acid and inhibited by angiotensin II (ANG II), adrenocorticotrophic hormone (ACTH), and forskolin. The activation and inhibition of TREK-1 was coupled to AZG cell hyperpolarization and depolarization, respectively. A second K2P channel, TASK-1 (KCNK3), was expressed at a lower density in AZG cells. Human AZG cells also express inwardly rectifying K + current(s) (K IR ) that include quasi-instantaneous and time-dependent components. This is the first report demonstrating the presence of K IR in whole cell recordings from AZG cells of any species. The time-dependent current was selectively inhibited by ANG II, and ACTH, identifying it as a G protein-coupled (GIRK) channel, most likely K IR 3.4 (KCNJ5). The quasi-instantaneous K IR current was not inhibited by ANG II or ACTH and may be a separate non-GIRK current. Finally, AZG cells express a voltage-gated, rapidly inactivating K + current whose properties identified as K V 1.4 (KCNA4), a conclusion confirmed by Northern blot. These findings demonstrate that human AZG cells express K2P and GIRK channels whose inhibition by ANG II and ACTH is likely coupled to depolarization-dependent secretion. They further demonstrate that human AZG K + channels differ fundamentally from the widely adopted rodent models for human aldosterone secretion. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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