Cloning and Characterization of an Olfactory Cyclic Nucleotide-gated Channel Expressed in Mouse Heart

Ruiz, María Luisa Bernal; London, Barry; Nadal-Ginard, B

doi:10.1006/jmcc.1996.0136

Cited by 30 publications

(14 citation statements)

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“…The A1 transcript was also detected in keratinocytes (310). Ruiz et al (350) could not detect by Northern analysis the A2 message in heart using several specific probes; however, using RNase protection ϩ RNA of heart, brain, lung, liver, skeletal muscle, and kidney. The RNase protection assay suggested the presence of A1 transcripts in retina, brain, lung, and spleen, but not in liver, heart, testis, and kidney.…”

Section: B Subunit Distribution In the Brain And Nonneuronal Tissuesmentioning

confidence: 99%

Cyclic Nucleotide-Gated Ion Channels

Kaupp

Seifert

2002

Physiological Reviews

1,026

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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Section: B Subunit Distribution In the Brain And Nonneuronal Tissuesmentioning

confidence: 99%

Cyclic Nucleotide-Gated Ion Channels

Kaupp

Seifert

2002

Physiological Reviews

1,026

1,027

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“…Thus, both the complex current records as well as the high conductance states we obtained from photomodified membrane patches could be explained by activation of protein ion channels especially if the following combination of events occurred: (1) the channel had brief open times, (2) channel conductance was small and (3) channel density was high. In light of the observation that recordings from membrane patches containing cyclic nucleotide-gated nonselective cation channels provide the best examples of current records similar to those we have obtained from photomodified cardiac membrane patches, it is of interest that it has been demonstrated recently that cardiac cells (and a variety of other cell types) express either the same or a channel closely related to these channels (25)(26)(27).…”

Section: Discussionmentioning

confidence: 70%

Photomodification of Cardiac Membrane: Chaotic Currents and High Conductance States in Isolated Patches

Tarr

Valenzeno

1998

Photochem & Photobiology

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We have demonstrated previously that photomodification permeabilizes cardiac cells as evidenced by activation of a whole-cell leak current. In this paper we report that photomodification induces in cell-attached and inside-out cardiac membrane patches a chaotic current. Unlike current recordings from many protein ion channels that show stepwise amplitude changes associated with open and closed states of the channel, the chaotic current consists of variable amplitude spike-like transitions. The amplitudes of these spikes can vary from tenths to tens of picoamperes at a constant transmembrane potential. We provide evidence that the chaotic current is transmembrane rather than trans-seal and has a voltage dependency expected for current flow through nonspecific conductance pathways. Photomodification can also induce high conductance states (greater than 500 pS) in cell-attached and inside-out patches. We present evidence that the high conductance state is also not related to seal breakdown. Our results suggest that both the chaotic current activity in and high conductance state of photomodified cardiac membrane patches result from the opening of many small conductance, nonspecific pathways through the membrane.

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“…NM_007724) (27) (Table 1). These oligos were annealed and ligated into linearized pSIREN-Shuttle (Clontech, Palo Alto, CA).…”

Section: Adenoviral Sirna Constructsmentioning

confidence: 97%

Frequency of Intrinsic Pulsatile Gonadotropin-Releasing Hormone Secretion Is Regulated by the Expression of Cyclic Nucleotide-Gated Channels in GT1 Cells

et al. 2007

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Cultures of endogenous GnRH neurons and the GT1 GnRH neuronal cell line release GnRH in pulses (intrinsic pulsatile release) with an interpulse frequency similar to that seen in castrated animals. In both GT1 cells and transgenic rats, lowering cAMP levels by expression of a phosphodiesterase decreased the frequency of intrinsic GnRH pulsatility. We asked whether the cyclic nucleotide-gated cation (CNG) channels expressed in GT1 cells participated in cAMP modulation of intrinsic GnRH pulsatility. Because expression of the CNGA2 subunit is essential for formation of functional CNG channels, we developed an adenovirus (Ad) vector expressing a short interference RNA (siRNA) to the CNGA2 subunit (Ad-CNG-siRNA) or as an infection control, to the coding region of luciferase (Ad-Luc-siRNA). Infection with the Ad-CNG-siRNA of COS cells transfected with a CNGA2 expression vector significantly inhibited CNGA2 protein levels by 74% by Western blot. Infection of GT1-1 cells with Ad-CNG-siRNA resulted in a 68% decrease in the levels of CNGA2 mRNA, a 44% decrease in protein levels, and a clear decrease in immunostaining with an antibody to CNGA2. Infection of GT1-1 cells with Ad-CNG-siRNA decreased spontaneous Ca2+ oscillations compared with Ad-Luc-siRNA-infected or uninfected cells by 71%. Furthermore infection with Ad-CNG-siRNA resulted in a 2-fold increase in the interpulse interval in GnRH secretion (49.4+/-9.1 min) compared with uninfected cells (25.9+/-2.5 min) or Ad-Luc-siRNA (29.3+/-2.8 min)-infected cells. These data provide the first direct evidence that the CNG channel is a downstream signaling molecule in the regulation of the frequency of intrinsic GnRH pulsatility by cAMP.

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Cloning and Characterization of an Olfactory Cyclic Nucleotide-gated Channel Expressed in Mouse Heart

Cited by 30 publications

References 0 publications

Cyclic Nucleotide-Gated Ion Channels

Cyclic Nucleotide-Gated Ion Channels

Photomodification of Cardiac Membrane: Chaotic Currents and High Conductance States in Isolated Patches

Frequency of Intrinsic Pulsatile Gonadotropin-Releasing Hormone Secretion Is Regulated by the Expression of Cyclic Nucleotide-Gated Channels in GT1 Cells

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