Inhibition of olfactory cyclic nucleotide‐activated current by calmodulin antagonists

Kleene, Steven J.

doi:10.1111/j.1476-5381.1994.tb14760.x

Cited by 37 publications

(23 citation statements)

References 41 publications

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“…Like the persistent currents through CNG channels activated by exogenous CO/cGMP (Leinders- Zufall et al, 1996) (Table 1), odor-induced background currents could be abolished reversibly by other CNG channel inhibitors besides Cd 2ϩ , such as the calmodulin inhibitor W-7 (100 M) (Fig. 2 D) (Kleene, 1994;Leinders-Zufall et al, 1995a). Furthermore, established background currents were inhibited by LY83583 (20 M) (Fig.…”

Section: Long-lasting Adaptation Is Indistinguishable From the Effectmentioning

confidence: 76%

Identification of a Long-Lasting Form of Odor Adaptation that Depends on the Carbon Monoxide/cGMP SecondMessenger System

Zufall

Leinders‐Zufall

1997

J. Neurosci.

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The diffusible messenger carbon monoxide (CO) has been proposed to mediate endogenous cyclic guanosine 3Ј,5Ј-monophosphate (cGMP) formation and sensory adaptation in vertebrate olfactory receptor neurons (ORNs). We have identified and characterized a long-lasting form of odor response adaptation (LLA) that operates at the level of isolated salamander ORNs and does not require any interactions from other cells. Manifestations of LLA are seen in reduced amplitude and prolonged kinetics of the cAMP-mediated excitatory odor response and the generation of a persistent current component that lasts for several minutes and is attributable to cyclic nucleotide-gated (CNG) channel activation by cGMP. Because these effects can be mimicked by micromolar amounts of exogenous cGMP or CO, we applied various inhibitors of cGMP formation. LLA is abolished selectively by heme oxygenase inhibitors known to prevent CO release and cGMP formation in ORNs, whereas odor excitation remains unaffected. In contrast, blockers of nitric oxide synthase are unable to eliminate LLA. Several controls rule out a contribution of nonspecific actions to the effects of CO inhibitors. The results indicate that endogenous CO/cGMP signals contribute to olfactory adaptation and underlie the control of gain and sensitivity of odor transduction. The findings offer a mechanism by which a single, brief odor stimulus can be translated into long-lasting intracellular changes that could play an important role in the perceptual adaptation to odors, and explain the longstanding puzzle that the olfactory CNG channels can be gated by both cAMP and cGMP.

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Section: Long-lasting Adaptation Is Indistinguishable From the Effectmentioning

confidence: 76%

Identification of a Long-Lasting Form of Odor Adaptation that Depends on the Carbon Monoxide/cGMP SecondMessenger System

Zufall

Leinders‐Zufall

1997

J. Neurosci.

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“…It is rather less effective at human P2X 7 receptors (307). This block is readily reversible and volt-age independent; calmidazolium blocks several other ion channels, including cyclic nucleotide-gated channels, although those effects require higher concentrations (251). (Fig.…”

Section: Antagonists/blockersmentioning

confidence: 98%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,691

128

3,397

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P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40–50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (∼280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., αβ-methylene ATP) and antagonists [e.g., 2′,3′- O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.

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“…A number of organic compounds have been reported to block current through CNG channels. The list of blockers includes L-cis-diltiazem (71,106,112,122,154,203,214,266,267,331,342,379); pimozide (306); amiloride and its derivative (112,307); tetracaine (109,110,362); polyamines (253,257,304); W-7, a calmodulin inhibitor (198,444); H-8, a PKA/ PKG inhibitor (410); and ruthenium red and neomycin (258). Except for pseudechetoxin, a peptide venom of the Australian King Brown snake (56), most inhibitors block the channel at micromolar concentrations.…”

Section: Pharmacologymentioning

confidence: 99%

Cyclic Nucleotide-Gated Ion Channels

Kaupp

Seifert

2002

Physiological Reviews

1,041

1,027

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Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila,and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

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Inhibition of olfactory cyclic nucleotide‐activated current by calmodulin antagonists

Abstract: 4 Neither W-7 nor trifluoperazine inhibited a Ca2"-activated Cl-current which also contributes to the odorant response. These compounds thus allow the two components of the olfactory receptor current to be discriminated.

Cited by 37 publications

References 41 publications

Identification of a Long-Lasting Form of Odor Adaptation that Depends on the Carbon Monoxide/cGMP SecondMessenger System

Identification of a Long-Lasting Form of Odor Adaptation that Depends on the Carbon Monoxide/cGMP SecondMessenger System

Molecular Physiology of P2X Receptors

Cyclic Nucleotide-Gated Ion Channels

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