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Potassium channel-based optogenetic silencing
摘要： Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photo-activated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this ‘PAC-K’ silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest.
关键词： Potassium channel,Neuronal silencing,Photo-activated adenylyl cyclases,Optogenetics,Cardiomyocyte excitation
更新于2025-09-23 15:21:21
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Remote Ischemia Influences the Responsiveness of the Retina: Observations in the Rat
摘要： Remote ischemic preconditioning (RIP) has been found to be protective of heart and brain against ischemic injury. We have tested the effects of RIP on retinal function using the electroretinogram. METHODS. Ischemia remote from the retina was induced in one hindlimb, using a pressure cuff applied for between 5 and 10 minutes. A temperature probe on the footpad con?rmed blockage of the circulation. To test the impact of RIP on retinal function, we recorded the dark-adapted ?ash electroretinogram (ERG) in four groups (n ? 5 per group) of Sprague-Dawley rats (sham, 5-minute, 10-minute, and 2 3 5-minute ischemia). Heart rate, breath rate, and peripheral oxygen saturation were monitored using infrared pulse oximetry. RESULTS. RIP increased both the a- and b-waves by up to 14%, more markedly after the longer periods (10 minutes or 2 3 5 minutes) of ischemia. The effect was tested up to 30 minutes after ischemia and retested at 1 week and 1 month. RIP did not appear to accelerate the initial stages of recovery from photopigment bleach. Systemic oxygen saturation, heart rate, and respiration did not vary consistently during or after remote ischemia. CONCLUSIONS. The effect of RIP on the ERG is a novel ?nding. Possible mechanisms of this effect are discussed and related to the idea of neuroprotection and to fundamentals of the electroretinogram.
关键词： remote ischemic preconditioning,ATP-sensitive potassium channel,dark adaptation,adenosine,electroretinogram,retina
更新于2025-09-09 09:28:46