Low-Conductance HCN1 Ion Channels Augment the Frequency Response of Rod and Cone Photoreceptors

Barrow, A.; Wu, Samuel M.

doi:10.1523/jneurosci.5746-08.2009

Cited by 76 publications

(105 citation statements)

References 52 publications

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“…We found that deletion of HCN1 leads to prolonged rod responses in the ERG, together with a reduced flicker fusion frequency 13 . We concluded that this is due to the lack of HCN1 in rods, which is also supported by ex vivo tiger salamander data 26 and have developed a concept and a set of hypotheses to examine the nature of this phenomenon. We found that HCN1 channel feedback is of crucial importance under conditions when both rods and cones are active.…”

Section: Discussionsupporting

confidence: 61%

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

et al. 2011

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Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into on-and oFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

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Section: Discussionsupporting

confidence: 61%

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

et al. 2011

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“…Further study can be performed to investigate the effect of overexpressing HCN channels in mESCs to elucidate the role of this I inst on the proliferation and cell cycle progression of mESCs. Nonetheless, hyperpolarization in the S phase is expected to result in one or both of the below scenarios: (1) activation of HCN channels and increase in I h which would in turn lead to depolarization and deactivation of the HCN channels, resulting in a decrease in I h at the end of S phase; (2) increase in the driving force for I inst which would in turn lead to depolarization, resulting in a decrease in driving force for I inst at the end of S phase. [4,6,26].…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells

Lau

Wong

Luo

et al. 2010

Pflugers Arch - Eur J Physiol

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Embryonic stem cells (ESCs) can uniquely proliferate indefinitely and differentiate into all cell lineages. ESCs may therefore provide an unlimited supply of cells for cell-based therapies. Previous study reported the presence of hyperpolarization-activated inward currents in undifferentiated mouse (m) ESCs, but the functional role of this hyperpolarization-activated current in mESCs is unknown. In this study, the role of this current in maintaining the proliferative capacity and the cell cycle progression of ESCs was investigated. In D3 mESCs, this hyperpolarization-activated inward current can be blocked by HCN channel blocker ZD7288. Application of the HCN channel blockers, cesium (1-10 mM) or ZD7288 (0.1-30 μM), attenuated cell proliferation in a concentration-dependent manner. Both HCN blockers were found to be non-cytotoxic to mESCs as determined by cell viability test. Interestingly, ZD7288 at 10 and 30 μM was found to decrease the proportion of cells in G(0)/G(1) phase and increase the proportion of cells in S phase. This suggests that this hyperpolarization-activated current can affect the cell cycle progression in mESCs. In summary, the present investigation suggests that ESC proliferation and cell cycle progression can be regulated by this hyperpolarization-activated current.

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“…Rod and cone synapses function as band-pass filters (Armstrong-Gold and Rieke, 2003;Burkhardt et al, 2007). Although several presynaptic factors, including gap-junctional coupling, voltage-gated conductances, and synaptic release kinetics, likely contribute to this (ArmstrongGold and Rieke, 2003;Zhang and Wu, 2005;Burkhardt et al, 2007;Barrow and Wu, 2009), the role of synaptic vesicle replenishment has not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

Hook¹,

Parmelee²,

Chen³

et al. 2014

J Cell Biol

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At the first synapse in the vertebrate visual pathway, light-evoked changes in photoreceptor membrane potential alter the rate of glutamate release onto second-order retinal neurons. This process depends on the synaptic ribbon, a specialized structure found at various sensory synapses, to provide a supply of primed vesicles for release. Calcium (Ca 2+ ) accelerates the replenishment of vesicles at cone ribbon synapses, but the mechanisms underlying this acceleration and its functional implications for vision are unknown. We studied vesicle replenishment using paired whole-cell recordings of cones and postsynaptic neurons in tiger salamander retinas and found that it involves two kinetic mechanisms, the faster of which was diminished by calmodulin (CaM) inhibitors. We developed an analytical model that can be applied to both conventional and ribbon synapses and showed that vesicle resupply is limited by a simple time constant,  = 1/(Ds), where D is the vesicle diffusion coefficient,  is the vesicle diameter,  is the vesicle density, and s is the probability of vesicle attachment. The combination of electrophysiological measurements, modeling, and total internal reflection fluorescence microscopy of single synaptic vesicles suggested that CaM speeds replenishment by enhancing vesicle attachment to the ribbon. Using electroretinogram and whole-cell recordings of light responses, we found that enhanced replenishment improves the ability of cone synapses to signal darkness after brief flashes of light and enhances the amplitude of responses to higherfrequency stimuli. By accelerating the resupply of vesicles to the ribbon, CaM extends the temporal range of synaptic transmission, allowing cones to transmit higher-frequency visual information to downstream neurons. Thus, the ability of the visual system to encode time-varying stimuli is shaped by the dynamics of vesicle replenishment at photoreceptor synaptic ribbons.

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Low-Conductance HCN1 Ion Channels Augment the Frequency Response of Rod and Cone Photoreceptors

Cited by 76 publications

References 52 publications

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

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