Kv3.1 to control accommodation due to the fact these channels have a high-threshold of activation and activate and deactivate rapidly (Gan and Kaczmarek, 1998). Most notably, photoswitchable SK2 channels had been applied to control the size of EPSPs in CA1 hippocampal neurons exactly where they are natively involved in dendritic repolarization following glutamate receptor-mediated depolarization (Fortin et al., 2011).OPTICAL Manage OF K2P POTASSIUM CHANNELS: TREKlight K2P channels are one of the most diverse and crucial subfamilies of potassium channels. They serve as a hub for the generation and regulation of a unfavorable resting membrane potential and hence,Potential neuronal applicationsReferencePhotocontrol of VmBanghart et al. (2004)Non-selective cation channel Voltage-gated V1/2 = -36 mVPhotocontrol of VmChambers et al. (2006)Kv1.3-H401YKvP374CtransVoltage-gated V1/2 = -30 mVPhotocontrol of AccomodationFortin et al. (2011)Kv3.KvE380CtransWeak inactivation V1/2 = -40 mVPhotocontrol of VmFortin et al. (2011)Kv7 .KvE257CtransM-type current V1/2 = -30 mV Ca2+ -activated Leak present pH-sensitive Comprehensive regulationPhotocontrol of Vm Photocontrol of M-current Photocontrol of afterhyperpolarization Photocontrol of VmFortin et al. (2011)SK2 TREK1/K2P 2.1 “TREKlight”SK K2PQ339C S121Ctrans cisFortin et al. (2011) Sandoz et al. (2012)TREK1/K2P 2.α-MSH 1 “SRARK-like”K2PK231CtransLeak present pH-sensitive In depth regulationPhotocontrol of VmSandoz et al.Corin (2012)TREKCK2PS121CcisLeak present pH-sensitive Substantial regulationPhotocontrol of native TREK1 ConductionSandoz et al.PMID:24428212 (2012)”TREK1-PCS”TASK3/K2P 9.K2PR73C or A74CtransLeak existing pH-sensitive In depth regulationPhotocontrol of VmSandoz et al. (2012)Frontiers in Molecular Neurosciencewww.frontiersin.orgApril 2013 | Volume 6 | Report six |Sandoz and LevitzOptogenetics of potassium channelscellular excitability. In addition to background roles as leak channels, K2P channels also play a central role in the dynamic response of cells to extracellular and intracellular signals as diverse as GPCR signaling, pH, and membrane stretch. TWIK-1-related K+ channel 1 (TREK1), a especially well-studied K2P channel, has been found to be involved in quite a few physiological processes such as neuroprotection against ischemia (Heurteaux et al., 2004), discomfort perception (Noel et al., 2011), and depression (Heurteaux et al., 2006). Constant with a proposed role for TREK1 in depression, TREK1 is inhibited by therapeutic doses of selective serotonin reuptake inhibitors (SSRIs) for instance fluoxetine (Prozac; Heurteaux et al., 2006; Sandoz et al., 2011) and spadin, a sortilin-derived peptide that also has antidepressive effects (Mazella et al., 2010). Together these properties recommend that TREK1 is an eye-catching pharmacological target for the development of new antidepressant drugs and provide motivation to get a deeper understanding of this channel’s function. Even so, regardless of the big interest in understanding the properties of K2P channels, it has been hard to decipher the precise physiological roles of person subtypes for instance TREK1. Because of this, this channel subfamily is specifically attractive for PTL-based optical handle. K2P channels are believed to be only weakly sensitive or insensitive to extracellular TEA (Noel et al., 2011). On the other hand, weakly TEA-sensitive channels may possibly nevertheless be sufficiently blocked by MAQ as a result of the higher successful concentration from the tethered quaternary ammonium ligand close to the pore inside the blocking state.