Dual action of leptin on rest‐firing and stimulated catecholamine release via phosphoinositide 3‐kinase‐driven BK channel up‐regulation in mouse chromaffin cells

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp6818-list-0001">Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite‐suppressing effect and, as such, exerts a relevant action on the adipo‐adrenal axis.Leptin has a dual action on adrenal mouse chromaffin cells both at rest and during stimulation. At rest, the adipokine inhibits the spontaneous firing of most cells by enhancing the probability of BK channel opening through the phosphoinositide 3‐kinase signalling cascade. This inhibitory effect is absent in db^–/db^– mice deprived of Ob receptors.During sustained stimulation, leptin preserves cell excitability by generating well‐adapted action potential (AP) trains of lower frequency and broader width and increases catecholamine secretion by increasing the size of the ready‐releasable pool and the rate of vesicle release.In conclusion, leptin dampens AP firing at rest but preserves AP firing and enhances catecholamine release during sustained stimulation, highlighting the importance of the adipo‐adrenal axis in the leptin‐mediated increase of sympathetic tone and catecholamine release.