Protective effects of TASK-3 (KCNK9) and related 2P K channels during cellular stress.
Tandem pore domain (or 2P) K channels form a recently isolated family of channels that are responsible for background K currents in excitable tissues. Previous studies have indicated that 2P K channel activity produces membrane hyperpolarization, which may offer protection from cellular insults. To study the effect of these channels in neuroprotection, we overexpressed pH-sensitive 2P K channels by transfecting the partially transformed C8 cell line with these channels. Tandem pore weak inward rectifier K channel (TWIK)-related acid-sensitive K channel 3 (TASK-3, KCNK9) as well as other pH sensitive 2P K channels (TASK-1 and TASK-2) enhanced cell viability by inhibiting the activation of intracellular apoptosis pathways. To explore the cellular basis for this protection in a more complex cellular environment, we infected cultured hippocampal slices with Sindbis virus constructs containing the coding sequences of these channels. Expression of TASK-3 throughout the hippocampal structure afforded neurons within the dentate and CA1 regions significant protection from an oxygen-glucose deprivation (OGD) injury. Neuroprotection within TASK-3 expressing slices was also enhanced by incubation with isoflurane. These results confirm a protective physiologic capability of TASK-3 and related 2P K channels, and suggest agents that enhance their activity, such as volatile anesthetics may intensify these protective effects.
Liu
Canhui
C
Severinghaus Anesthesia Laboratory, Department of Anesthesia and Perioperative Care, University of California San Francisco, 513 Parnassus Ave., Room S-261, Box 0542, San Francisco, CA 94143-0542, United States.
Cotten
Joseph F
JF
Schuyler
Jennifer A
JA
Fahlman
Christian S
CS
Au
John D
JD
Bickler
Philip E
PE
Yost
C Spencer
CS
D000693:Anaerobiosis / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C498739:Kcnk5 protein, mouse; C498740:Kcnk5 protein, rat; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C420132:potassium channel subfamily K member 3