Cooperativity in cyclic nucleotide-gated ion channels.

Pugh, Edward N.

doi:10.1085/jgp.107.2.165

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…Cyclic nucleotide-gated (CNG) channels are members of the voltage-gated channel family and are the subject of many reviews (Finn et al, 1996;Pugh, 1996;Zagotta and Siegelbaum, 1996;Karpen, 1997;Li et al, 1997;Molday and Molday, 1998;Biel et al, 1999;Broillet and Firestein, 1999;Frings, 1999;Richards and Gordon, 2000;Bradley et al, 2001;Flynn et al, 2001;Kaupp and Seifert, 2002;Warren and Molday, 2002;Zimmerman, 2002;Matulef and Zagotta, 2003). CNG channels that mediate the light response in retinal rods are nonselective cation channels that are weakly voltage dependent and are thought to be tetramers consisting of one ␤ -and three ␣ -subunits.…”

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confidence: 99%

All-trans-retinal Is a Closed-state Inhibitor of Rod Cyclic Nucleotide–gated Ion Channels

McCabe

Pelosi

Tetreault

et al. 2004

The Journal of General Physiology

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Rod vision begins when 11-cis-retinal absorbs a photon and isomerizes to all-trans-retinal (ATR) within the photopigment, rhodopsin. Photoactivated rhodopsin triggers an enzyme cascade that lowers the concentration of cGMP, thereby closing cyclic nucleotide–gated (CNG) ion channels. After isomerization, ATR dissociates from rhodopsin, and after a bright light, this release is expected to produce a large surge of ATR near the CNG channels. Using excised patches from Xenopus oocytes, we recently showed that ATR shuts down cloned rod CNG channels, and that this inhibition occurs in the nanomolar range (aqueous concentration) at near-physiological concentrations of cGMP. Here we further characterize the ATR effect and present mechanistic information. ATR was found to decrease the apparent cGMP affinity, as well as the maximum current at saturating cGMP. When ATR was applied to outside-out patches, inhibition was much slower and less effective than when it was applied to inside-out patches, suggesting that ATR requires access to the intracellular surface of the channel or membrane. The apparent ATR affinity and maximal inhibition of heteromeric (CNGA1/CNGB1) channels was similar to that of homomeric (CNGA1) channels. Single-channel and multichannel data suggest that channel inhibition by ATR is reversible. Inhibition by ATR was not voltage dependent, and the form of its dose–response relation suggested multiple ATR molecules interacting per channel. Modeling of the data obtained with cAMP and cGMP suggests that ATR acts by interfering with the allosteric opening transition of the channel and that it prefers closed, unliganded channels. It remains to be determined whether ATR acts directly on the channel protein or instead alters channel–bilayer interactions.

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confidence: 99%

All-trans-retinal Is a Closed-state Inhibitor of Rod Cyclic Nucleotide–gated Ion Channels

McCabe

Pelosi

Tetreault

et al. 2004

The Journal of General Physiology

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“…Cyclic nucleotide–gated (CNG) channels are heteromultimeric membrane proteins that share features in common with voltage-dependent Na + and K + channels ( Chen et al, 1993 ; Bradley et al, 1994 ; Liman and Buck, 1994 ; Menini, 1995 ; Pugh, 1996 ). They play a well known role in sensory transduction in photoreceptors and olfactory receptors ( Yau and Baylor, 1989 ; Zufall et al, 1994 ; Zufall, 1996 ; Zagotta and Siegelbaum, 1996 ; Finn et al, 1996 ).…”

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confidence: 99%

Cyclic GMP–gated Channels in a Sympathetic Neuron Cell Line

Thompson

1997

The Journal of General Physiology

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The stimulation of IP3 production by muscarinic agonists causes both intracellular Ca2+ release and activation of a voltage-independent cation current in differentiated N1E-115 cells, a neuroblastoma cell line derived from mouse sympathetic ganglia. Earlier work showed that the membrane current requires an increase in 3′,5′-cyclic guanosine monophosphate (cGMP) produced through the NO-synthase/guanylyl cyclase cascade and suggested that the cells may express cyclic nucleotide–gated ion channels. This was tested using patch clamp methods. The membrane permeable cGMP analogue, 8-br-cGMP, activates Na+ permeable channels in cell attached patches. Single channel currents were recorded in excised patches bathed in symmetrical Na+ solutions. cGMP-dependent single channel activity consists of prolonged bursts of rapid openings and closings that continue without desensitization. The rate of occurrence of bursts as well as the burst length increase with cGMP concentration. The unitary conductance in symmetrical 160 mM Na+ is 47 pS and is independent of voltage in the range −50 to +50 mV. There is no apparent effect of voltage on opening probability. The dose response curve relating cGMP concentration to channel opening probability is fit by the Hill equation assuming an apparent K D of 10 μm and a Hill coefficient of 2. In contrast, cAMP failed to activate the channel at concentrations as high as 100 μm. Cyclic nucleotide gated (CNG) channels in N1E-115 cells share a number of properties with CNG channels in sensory receptors. Their presence in neuronal cells provides a mechanism by which activation of the NO/cGMP pathway by G-protein–coupled neurotransmitter receptors can directly modify Ca2+ influx and electrical excitability. In N1E-115 cells, Ca2+ entry by this pathway is necessary to refill the IP3-sensitive intracellular Ca2+ pool during repeated stimulation and CNG channels may play a similar role in other neurons.

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