Tandem-pore domain potassium channels are functionally expressed in retinal (Müller) glial cells.
Tandem-pore domain (2P-domain) K+-channels regulate neuronal excitability, but their function in glia, particularly, in retinal glial cells, is unclear. We have previously demonstrated the immunocytochemical localization of the 2P-domain K+ channels TASK-1 and TASK-2 in retinal Müller glial cells of amphibians. The purpose of the present study was to determine whether these channels were functional, by employing whole-cell recording from frog and mammalian (guinea pig, rat and mouse) Müller cells and confocal microscopy to monitor swelling in rat Müller cells. TASK-like immunolabel was localized in these cells. The currents mediated by 2P-domain channels were studied in isolation after blocking Kir, K(A), K(D), and BK channels. The remaining cell conductance was mostly outward and was depressed by acid pH, bupivacaine, methanandamide, quinine, and clofilium, and activated by alkaline pH in a manner consistent with that described for TASK channels. Arachidonic acid (an activator of TREK channels) had no effect on this conductance. Blockade of the conductance with bupivacaine depolarized the Müller cell membrane potential by about 50%. In slices of the rat retina, adenosine inhibited osmotic glial cell swelling via activation of A1 receptors and subsequent opening of 2P-domain K+ channels. The swelling was strongly increased by clofilium and quinine (inhibitors of 2P-domain K+ channels). These data suggest that 2P-domain K+ channels are involved in homeostasis of glial cell volume, in activity-dependent spatial K+ buffering and may play a role in maintenance of a hyperpolarized membrane potential especially in conditions where Kir channels are blocked or downregulated.
Skatchkov
S N
SN
CMBN, Department of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamón, Puerto Rico 00960-6032. sergueis50@yahoo.com
Eaton
M J
MJ
Shuba
Y M
YM
Kucheryavykh
Y V
YV
Derst
C
C
Veh
R W
RW
Wurm
A
A
Iandiev
I
I
Pannicke
T
T
Bringmann
A
A
Reichenbach
A
A
D000818:Animals; D048429:Cell Size; D004594:Electrophysiology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009997:Osmotic Pressure; D010477:Perfusion; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis*; D011894:Rana pipiens; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000378:metabolism*
D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain