Abstract
BackgroundTwo-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. However, physiological function of TWIK-1, the first identified member of the mammalian K2P channel family, in neuronal cells is largely unknown.ResultsWe found that TWIK-1 proteins were expressed and localized mainly in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs) rather than in distal dendrites or mossy fibers. Gene silencing demonstrates that the outwardly rectifying K+ current density was reduced in TWIK-1-deficient granule cells. TWIK-1 deficiency caused a depolarizing shift in the resting membrane potential (RMP) of DGGCs and enhanced their firing rate in response to depolarizing current injections. Through perforant path stimulation, TWIK-1-deficient granule cells showed altered signal input-output properties with larger EPSP amplitude values and increased spiking compared to control DGGCs. In addition, supra-maximal perforant path stimulation evoked a graded burst discharge in 44% of TWIK-1-deficient cells, which implies impairment of EPSP-spike coupling.ConclusionsThese results showed that TWIK-1 is functionally expressed in DGGCs and contributes to the intrinsic excitability of these cells. The TWIK-1 channel is involved in establishing the RMP of DGGCs; it attenuates sub-threshold depolarization of the cells during neuronal activity, and contributes to EPSP-spike coupling in perforant path-to-granule cell synaptic transmission.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-014-0080-z) contains supplementary material, which is available to authorized users.
Highlights
Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability
TWIK-1 is expressed in dentate granule cells of mouse hippocampus TWIK-1 mRNAs are reportedly expressed in dentate gyrus granule cells (DGGCs) [16,17]
We found that TWIK-1 channels are broadly expressed in the hippocampus, including dentate gyrus (DG) and CA1-3 regions (Figure 1A)
Summary
Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. physiological function of TWIK-1, the first identified member of the mammalian K2P channel family, in neuronal cells is largely unknown. Two-pore domain K+ (K2P) channels are major contributors to background potassium conductance in cells and control resting membrane potential (RMP) as well as cellular excitability [1]. These K2P channels are modulated by a large variety of physical and chemical stimuli including temperature, membrane stretch, pH, polyunsaturated fatty acids, hormones and neurotransmitters. We have recently demonstrated that TWIK-1/TREK-1 heterodimers mediate a passive conductance in astrocytes [9]. These observations strongly suggest about important physiological roles for TWIK-1
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