Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric oxide and reactive oxygen species.
This study firstly shows with in situ hybridization on human pancreas that TALK-1 and TALK-2, two members of the 2P domain potassium channel (K(2P)) family, are highly and specifically expressed in the exocrine pancreas and absent in Langherans islets. On the contrary, expression of TASK-2 in mouse pancreas is found both in the exocrine pancreas and in the Langherans islets. This study also shows that TALK-1 and TALK-2 channels, expressed in Xenopus oocytes, are strongly and specifically activated by nitric oxide (obtained with a mixture of sodium nitroprussate (SNP) and dithiothreitol (DTT)), superoxide anion (obtained with xanthine and xanthine oxidase) and singlet oxygen (obtained upon photoactivation of rose bengal, and with chloramine T). Other nitric oxide and reactive oxygen species (NOS and ROS) donors, as well as reducing conditions were found to be ineffective on TALK-1, TALK-2 and TASK-2 (sin-1, angeli's salt, SNP alone, tBHP, H(2)O(2), and DTT). These results suggest that, in the exocrine pancreas, specific members of the NOS and ROS families could act as endogenous modulators of TALK channels with a role in normal secretion as well as in disease states such as acute pancreatitis and apoptosis.
Duprat
F
F
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR 6097, 660 route des Lucioles, Sophia Antipolis, 06560 Vabonne, France.
Girard
C
C
Jarretou
G
G
Lazdunski
M
M
D000818:Animals; D004594:Electrophysiology; D006801:Humans; D017665:Hydroxyl Radical / Q000494:pharmacology; D017403:In Situ Hybridization; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010179:Pancreas / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects*; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D014982:Xenopus laevis
C477398:KCNK16 protein, human; C410295:KCNK5 protein, human; C498739:Kcnk5 protein, mouse; D016877:Oxidants; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D017665:Hydroxyl Radical