RT Journal Article
SR Electronic
T1 Hydrogen Sulfide as an Allosteric Modulator of ATP-Sensitive Potassium Channels in Colonic Inflammation
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 294
OP 306
DO 10.1124/mol.112.081596
VO 83
IS 1
A1 Aravind R. Gade
A1 Minho Kang
A1 Hamid I. Akbarali
YR 2013
UL http://molpharm.aspetjournals.org/content/83/1/294.abstract
AB The ATP-sensitive potassium channel (KATP) in mouse colonic smooth muscle cell is a complex containing a pore-forming subunit (Kir6.1) and a sulfonylurea receptor subunit (SUR2B). These channels contribute to the cellular excitability of smooth muscle cells and hence regulate the motility patterns in the colon. Whole-cell voltage-clamp techniques were used to study the alterations in KATP channels in smooth muscle cells in experimental colitis. Colonic inflammation was induced in BALB/C mice after intracolonic administration of trinitrobenzene sulfonic acid. KATP currents were measured at a holding potential of −60 mV in high K+ external solution. The concentration response to levcromakalim (LEVC), a KATP channel opener, was significantly shifted to the left in the inflamed smooth-muscle cells. Both the potency and maximal currents induced by LEVC were enhanced in inflammation. The EC50 values in control were 6259 nM (n = 10) and 422 nM (n = 8) in inflamed colon, and the maximal currents were 9.9 ± 0.71 pA/pF (60 μM) in control and 39.7 ± 8.8 pA/pF (3 μM) after inflammation. As was seen with LEVC, the potency and efficacy of sodium hydrogen sulfide (NaHS) (10–1000 μM) on KATP currents were significantly greater in inflamed colon compared with controls. In control cells, pretreatment with 100 µM NaHS shifted the EC50 for LEV-induced currents from 2838 (n = 6) to 154 (n = 8) nM. Sulfhydration of sulfonylurea receptor 2B (SUR2B) was induced by NaHS and colonic inflammation. These data suggest that sulfhydration of SUR2B induces allosteric modulation of KATP currents in colonic inflammation.