| First Author | Pan NC | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 446 |
| Issue | 1 | Pages | 316-21 |
| PubMed ID | 24602615 | Mgi Jnum | J:207964 |
| Mgi Id | MGI:5560378 | Doi | 10.1016/j.bbrc.2014.02.110 |
| Citation | Pan NC, et al. (2014) Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells. Biochem Biophys Res Commun 446(1):316-21 |
| abstractText | The large conductance Ca(2+)-activated K(+) (BK) channels are widely distributed in the brain, and act as intracellular calcium sensors in neurons. They play an important feedback role in controlling Ca(2+) flux and Ca(2+)-dependent processes, including neurotransmitter release and cellular excitability. In this study, the effects of the neuropeptide galanin on BK channels were examined by determining the whole-cell currents and single-channel activities in human embryonic kidney (HEK293) cells co-expressing GalR2 and the BK alpha subunit. Galanin enhanced the currents of BK channels, in a concentration-dependent and PTX-independent manner, with an ED50 value of 71.8+/-16.9nM. This activation was mediated by GalR2, since its agonist AR-M1896 mimicked the effect of galanin, and since galanin did not facilitate BK currents in cells co-expressing cDNAs of BK and GalR1 or GalR3. The galanin-induced BK current persisted after replacement with Ca(2+)-free solution, suggesting that extracellular Ca(2+) is not essential. Chelating intracellular Ca(2+) by either the slow Ca(2+) buffer EGTA or the fast Ca(2+) buffer BAPTA abolished galanin-mediated activation of BK channels, indicating the important role of intracellular Ca(2+). The role of Ca(2+) efflux from the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) was confirmed by application of thapsigargin, an irreversible inhibitor that depletes Ca(2+) from SR/ER. Moreover, the inositol-1,4,5-triphosphate receptor (IP3R) was identified as the mediator responsible for increased intracellular Ca(2+) activating BK channels. Taken together, activation of GalR2 leads to elevation of intracellular Ca(2+) is due to Ca(2+) efflux from ER through IP3R sequentially opening BK channels. |
