Abstract
Two-pore domain (K2P) potassium channels perform essential roles in neuronal function. These channels produce background leak type potassium currents that act to regulate resting membrane potential and levels of cellular excitability. 15 different K2P channels have been identified in mammals and these channels perform important roles in a wide number of physiological systems. However, to date there is only limited data available concerning the expression and role of K2P channels in the retina. In this study we conduct the first comprehensive study of K2P channel expression in the retina. Our data show that K2P channels are widely expressed in the mouse retina, with variations in expression detected at different times of day and throughout postnatal development. The highest levels of K2P channel expression are observed for Müller cells (TWIK-1, TASK-3, TRAAK, and TREK-2) and retinal ganglion cells (TASK-1, TREK-1, TWIK-1, TWIK-2 and TWIK-3). These data offer new insight into the channels that regulate the resting membrane potential and electrical activity of retinal cells, and suggests that K2P channels are well placed to act as central regulators of visual signalling pathways. The prominent role of K2P channels in neuroprotection offers novel avenues of research into the treatment of common retinal diseases.
Highlights
With an enlarged scale to highlight the expression of K2P channels expressed at lower levels
The highest levels of mRNA expression were detected for TWIK-1, TASK-1, TRAAK, and TRESK, with mRNA transcripts for TWIK-2, TWIK-3, Target KCNK1 (TWIK-1) KCNK2 (TREK-1), TREK-2, K2P channel TWIK-1 TWIK-2 TWIK-3 TASK-1 TASK-3 TREK-1 TREK-2 TRAAK TRESK TASK-2
For the majority of K2P channels, including TWIK-2, TREK-1, TRAAK, TASK-1, TASK-3, TASK-5, and TRESK, a clear up regulation of mRNA expression was detected throughout postnatal development with expression typically reaching maximal levels by P14
Summary
This study represents the first comprehensive investigation of two-pore domain (K2P) K+ ion channel expression within the mammalian retina. Glutamate is the key neurotransmitter by which bipolar cells transmit rod and cone derived signals to RGCs75–77, and a previous study has described the presence of a glutamate sensitive background leak type K+ current in cultured mouse RGCs with properties of a TASK like current, most likely TASK-1 or TASK-378 Inhibition of this TASK-type current by the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) results in the depolarisation of retinal ganglion cells and increased levels of action potential firing, suggesting a significant role for TASK type channels in the regulation of RGC excitability by glutamate. It is possible that these cell types show less functional reliance on K+ leak currents than typical spike firing neurones, such as RGCs. Our data do indicate the expression of at least four distinct K2P channels within Müller cells, including TWIK-1, TASK-3, TRAAK, and TREK-2. Based on our data it is possible that TWIK-1, TASK-3, TRAAK and TREK-2 may perform similar
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