Mechanisms of tonic, graded release: lessons from the vertebrate photoreceptor

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

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Biosynthesis and Morphogenesis of Outer Segment Membranes in Vertebrate Photoreceptor Cells

Cell Biology of the Eye ◽

10.1016/b978-0-12-483180-3.50015-0 ◽

1982 ◽

pp. 475-531 ◽

Cited By ~ 19

Author(s):

DAVID S. PAPERMASTER ◽

BARBARA G. SCHNEIDER

Keyword(s):

Outer Segment ◽

Photoreceptor Cells ◽

Vertebrate Photoreceptor

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Hydrogen ion effects of the vertebrate photoreceptor

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(78)90362-4 ◽

1978 ◽

Vol 188 (1) ◽

pp. 105-113 ◽

Cited By ~ 13

Author(s):

Clark Gedney ◽

Sanford E. Ostroy

Keyword(s):

Hydrogen Ion ◽

Vertebrate Photoreceptor ◽

Ion Effects

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Spike-Mediated and Graded Inhibitory Synaptic Transmission Between Leech Interneurons: Evidence for Shared Release Sites

Journal of Neurophysiology ◽

10.1152/jn.01094.2005 ◽

2006 ◽

Vol 96 (1) ◽

pp. 235-251 ◽

Cited By ~ 10

Author(s):

Andrei I. Ivanov ◽

Ronald L. Calabrese

Keyword(s):

Synaptic Transmission ◽

Synaptic Vesicles ◽

Low Voltage ◽

Release Site ◽

High Threshold ◽

Channel Blockers ◽

Ca Channel ◽

Ca Channels ◽

Inhibitory Synaptic Transmission ◽

Graded Release

Inhibitory synaptic transmission between leech heart interneurons consist of two components: graded, gated by Ca2+ entering by low-threshold [low-voltage–activated (LVA)] Ca channels and spike-mediated, gated by Ca2+ entering by high-threshold [high-voltage–activated (HVA)] Ca channels. Changes in presynaptic background Ca2+ produced by Ca2+ influx through LVA channels modulate spike-mediated transmission, suggesting LVA channels have access to release sites controlled by HVA channels. Here we explore whether spike-mediated and graded transmission can use the same release sites and thus how Ca2+ influx by HVA and LVA Ca channels might interact to evoke neurotransmitter release. We recorded pre- and postsynaptic currents from voltage-clamped heart interneurons bathed in 0 mM Na+/5 mM Ca2+ saline. Using different stimulating paradigms and inorganic Ca channel blockers, we show that strong graded synaptic transmission can occlude high-threshold/spike-mediated synaptic transmission when evoked simultaneously. Suppression of LVA Ca currents diminishes graded release and concomitantly increases the ability of Ca2+ entering by HVA channels to release transmitter. Uncaging of Ca chelator corroborates that graded release occludes spike-mediated transmission. Our results indicate that both graded and spike-mediated synaptic transmission depend on the same readily releasable pool of synaptic vesicles. Thus Ca2+, entering cells through different Ca channels (LVA and HVA), acts to gate release of the same synaptic vesicles. The data argue for a closer location of HVA Ca channels to release sites than LVA Ca channels. The results are summarized in a conceptual model of a heart interneuron release site.

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Localization and properties of bovine photoreceptor 5'-nucleotidase

AJP Cell Physiology ◽

10.1152/ajpcell.1983.244.1.c89 ◽

1983 ◽

Vol 244 (1) ◽

pp. C89-C99 ◽

Cited By ~ 64

Author(s):

L. W. Yu ◽

R. S. Fager

Keyword(s):

Time Constant ◽

Receptor Potential ◽

Cell Receptor ◽

Nucleotidase Activity ◽

Visual Transduction ◽

Physiological Conditions ◽

Cytoplasmic Surface ◽

Vertebrate Photoreceptor ◽

Ph Range ◽

Rod Cell

The main light-activated enzyme of the vertebrate photoreceptor is cGMP phosphodiesterase, whose product is GMP. GMP would be broken down to guanosine by the enzyme 5'-nucleotidase on the cytoplasmic (extradiscal) surface of the disks. The presence of 5'-nucleotidase on the cytoplasmic surface was verified by using sucrose continuous gradients to show its association with the photoreceptors and by using disk preparation and concanavalin A binding to demonstrate its presence on the extradiscal surface. Further studies using detergents and freeze-thaw showed that an even higher 5'-nucleotidase activity is present on the intradiscal surface; however, it is the smaller cytoplasmic surface activity that is potentially relevant to the physiology. The 5'-nucleotidase on the extradiscal surface is light insensitive, has a broad optimal pH range, shows a divalent cation dependence, and is competitively inhibited by nucleoside di- and triphosphates. When the data determined experimentally were extrapolated to physiological conditions, we obtained a decay time constant for GMP breakdown by 5'-nucleotidase in the range of 0.4 to 1.06 s. This time constant is in the range of the time constants of the fall of rod cell receptor potential, suggesting a possible role for GMP level in visual transduction.

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Noxious Cutaneous Thermal Stimuli Induce a Graded Release of Endogenous Substance P in the Spinal Cord: Imaging Peptide ActionIn Vivo

Journal of Neuroscience ◽

10.1523/jneurosci.17-15-05921.1997 ◽

1997 ◽

Vol 17 (15) ◽

pp. 5921-5927 ◽

Cited By ~ 116

Author(s):

Brian J. Allen ◽

Scott D. Rogers ◽

Joseph R. Ghilardi ◽

Patrick M. Menning ◽

Michael A. Kuskowski ◽

...

Keyword(s):

Spinal Cord ◽

Substance P ◽

Endogenous Substance ◽

Graded Release ◽

Thermal Stimuli ◽

Spinal Cord Imaging

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Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors

The Journal of General Physiology ◽

10.1085/jgp.200910394 ◽

2010 ◽

Vol 135 (4) ◽

pp. 355-366 ◽

Cited By ~ 16

Author(s):

Hugh R. Matthews ◽

Alapakkam P. Sampath

Keyword(s):

Time Constant ◽

Light Adaptation ◽

Light Response ◽

Response Duration ◽

Photoreceptor Cells ◽

Quenching Rate ◽

Vertebrate Photoreceptor ◽

Cone Response ◽

Rate Limiting ◽

Phototransduction Cascade

The time scale of the photoresponse in photoreceptor cells is set by the slowest of the steps that quench the light-induced activity of the phototransduction cascade. In vertebrate photoreceptor cells, this rate-limiting reaction is thought to be either shutoff of catalytic activity in the photopigment or shutoff of the pigment's effector, the transducin-GTP–phosphodiesterase complex. In suction pipette recordings from isolated salamander L-cones, we found that preventing changes in internal [Ca2+] delayed the recovery of the light response and prolonged the dominant time constant for recovery. Evidence that the Ca2+-sensitive step involved the pigment itself was provided by the observation that removal of Cl− from the pigment's anion-binding site accelerated the dominant time constant for response recovery. Collectively, these observations indicate that in L-cones, unlike amphibian rods where the dominant time constant is insensitive to [Ca2+], pigment quenching rate limits recovery and provides an additional mechanism for modulating the cone response during light adaptation.

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