Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism.

Koch, K W; Kaupp, U. Benjamin

doi:10.1016/s0021-9258(18)88849-4

Cited by 212 publications

(59 citation statements)

References 65 publications

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“…This was not seen in intact OS or OS-IS, probably because the added 8 bromo-cGMP did not gain access (on a time scale of seconds) to the gating site located in the cytoplasm (cf. Koch and Kaupp, 1985 ;Fesenko et al, 1985 ;Schnetkamp, 1986). The cGMP-dependent Ca 21 flux was not observed in the TMA medium, but required the presence of alkali cations, as observed in bovine disks (Koch and Kaupp, 1985).…”

Section: Contained Predominantly Inside Disksmentioning

confidence: 81%

Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors.

Schnetkamp¹,

Bownds²

1987

The Journal of General Physiology

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We have examined the Cal ' content and pathways of Ca l ' transport in frog rod outer segments using the Ca"-indicating dye arsenazo III . The experiments employed suspensions of outer segments of truncated, but physiologically functional, frog rods (OS-IS), intact isolated outer segments (intact OS), and leaky outer segments (leaky OS with a plasma membrane leaky to small solutes, but with sealed disk membranes). We observed the following . (a) Intact OS or OS-IS isolated and purified in Percoll-Ringer's solution contained an average of 2.2 mM total Ca 21, while leaky OS contained 2 .0 mM total Ca 21 . This suggests that most of the Cat' in OS-IS is contained inside OS disks . (b) Phosphodiesterase inhibitors increased the Ca t' content to^-4 .2 mM in intact OS or OS-IS, whereas the Cat ' content of leaky OS was not altered. (c) Na-Ca exchange was the dominant pathway for Ca t' efflux in both intact and leaky OS/OS-IS . The rate of Na-Ca exchange in intact OS/OS-IS was halfmaximal between 30 and 50 mM Na' ; at 50 mM Na', this amounted to 5.8 X 10' Cat'/OS . s or 0.05 mM total Ca t '/s. This is much larger than the Call component of the dark current . (d) Other alkali cations could not replace Na' in Na-Ca exchange in either OS-IS or leaky OS . They inhibited the rate of NaCa exchange (K >_ Rb > Cs ? Li > TMA) and, as the inhibition became greater, a delay developed in the onset of Na-Ca exchange. The inhibition of Na-Ca exchange by alkali cations correlates with the prolonged duration of the photoresponse induced by these cations (Hodgkin, A . L., P. A . McNaughton, and B. J. Nunn. 1985. journal of Physiology. 358 :447-468) . (e) In addition to Na-Ca exchange, disk membranes in leaky OS showed a second pathway of Ca t' transport activated by cyclic GMP (cGMP) . The cGMP-activated pathway required the presence of alkali cations and had a maximal rate of 9 .7 X 10 6 Cat'/OS-s. cGMP caused the release of only 30% of the total Ca l' from leaky OS . The rate of Na-Ca exchange in leaky OS amounted to 1 .9 X 10' Ca 21/ OS-s . (f) Even though the ratio of plasma to disk membrane surface area in frog OS is -1/100, the measured Cal ' flux across the plasma membrane would be expected to change the cytoplasmic Cat' levels three times faster than Call fluxes across the disk membrane .Address reprint requests to Dr . Paul P. M . Schnetkamp,

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Section: Contained Predominantly Inside Disksmentioning

confidence: 81%

Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors.

Schnetkamp¹,

Bownds²

1987

The Journal of General Physiology

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“…The release of Ca ++ from ROS and OS-IS suspensions was determined spectroscopically with the Ca++-indicating dye arsenazo III. For details of the spectroscopic assay for Ca ++ fluxes in frog and bovine rods, see Koch and Kaupp (1985), Schnetkamp (1986), and Schnetkamp and Bownds (1987). ROS and OS-IS bands were removed from the gradient (-3 ml) and each was diluted with 2 vol of 125 mM tetramethylammonium-chloride (TMA-CI) and 20 mM HEPES, adjusted to pH 7.4 with arginine.…”

Section: Ca ++ Flux Measurements In Frog Ros and Os-ismentioning

confidence: 99%

“…DCPA proved to be a much more effective inhibitor of a cGMP-induced Ca ++ efflux from frog rod disk membranes than expected. The action of cGMP on Ca ++ flux has been described previously for bovine and frog rod disk membranes (Caretta and Cavaggioni, 1983;Koch and Kaupp, 1985;Schnetkamp and Bownds, 1987). Fig.…”

Section: Dcpa Inhibition Of a Cgmp-induced Ca ++ Releasementioning

confidence: 99%

“…The inverted photoresponse described above was not blocked by the addition of 50 ~tM diltiazem to the 10 nM Ca ++ Ringer's containing 50 uM DCPA (in three OS-IS; data not shown). Diltiazem is the only other known antagonist of the cGMP-activated Ca ++ efflux (Koch and Kaupp, 1985) and conductance (Stern et al, 1986).…”

Section: Mechanism Of Dcpa Inhibitionmentioning

confidence: 99%

“…Recently, an inhibitor of the light-regulated conductance has been identified. Kaupp and his colleagues have found that l-cis-diltiazem blocks a cyclic GMP-activated conductance in excised patches of rod membrane (Stern et al, 1986), as well as a cGMP-induced Ca ++ release from rod disk membranes (Koch and Kaupp, 1985). However, when applied externally to the intact rod, l-cisdiltiazem only suppresses the light-regulated current by threefold (Stern et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

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A derivative of amiloride blocks both the light-regulated and cyclic GMP-regulated conductances in rod photoreceptors.

Nicol

Schnetkamp

Saimi

et al. 1987

The Journal of General Physiology

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Vertebrate rod photoreceptors in the dark maintain an inward current across the outer segment membrane. The photoresponse results from a light-induced suppression of this dark current. The light-regulated current is not sensitive to either tetrodotoxin or amiloride, potent blockers of Na+ channels. Here, we report that a derivative of amiloride, 3',4'-dichlorobenzamil (DCPA), completely suppresses the dark current and light response recorded from rod photoreceptors. DCPA also blocks a cyclic GMP-activated current in excised patches of rod plasma membrane and a cGMP-induced Ca++ flux from rod disk membranes. These results are consistent with the notion that the Ca++ flux mechanism in the disk membrane and the light-regulated conductance in the plasma membrane are identical. DCPA also inhibits the Na/Ca exchange mechanism in intact rods, but at a 5-10-fold-higher concentration than is required to block the cGMP-activated flux and current. The blocking action of DCPA in 10 nM Ca++ is different from that in 1 mM Ca++, which suggests either that the conductance state of the light-regulated channel may be modified in high and low concentrations of Ca++, or that there may be two ionic channels in the rod outer segment membrane.

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[7‐(Dialkylamino)coumarin‐4‐yl]methyl‐Caged Compounds as Ultrafast and Effective Long‐Wavelength Phototriggers of 8Bromo‐Substituted Cyclic Nucleotides

et al. 2003

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[7-(Dimethylamino)coumarin-4-yl]methyl (DMACM) and [7-(diethylamino)coumarin-4-yl]methyl (DEACM) esters of 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) are described as novel caged compounds for 8-bromo-substituted cyclic nucleotides. Synthesis is accomplished by treatment of the free acids of the cyclic nucleotides with the corresponding 7(dialkylamino)-substituted 4(diazomethyl)coumarins. Irradiation of the DMACM- and DEACM-caged cyclic nucleotides with UV light stimulates the release of the cyclic nucleotides within roughly a nanosecond. The new caged compounds are resistant to hydrolysis in aqueous buffers and exhibit long-wavelength absorption properties with maxima at 400 nm, high extinction coefficients, and high quantum yields (0.15-0.31). Their favorable properties render these compounds the most efficient and rapid phototriggers of 8-bromo-substituted cyclic nucleotides known. The usefulness of the compounds for physiological studies under nondamaging light conditions was examined in HEK293 cells expressing the alpha subunit of the cyclic-nucleotide-gated (CNG) channel of cone photoreceptors (CNGA3) and of olfactory neurons (CNGA2) by using confocal laser scanning microscopy and the patch clamp technique.

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Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism.

Cited by 212 publications

References 65 publications

Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors.

Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors.

A derivative of amiloride blocks both the light-regulated and cyclic GMP-regulated conductances in rod photoreceptors.

[7‐(Dialkylamino)coumarin‐4‐yl]methyl‐Caged Compounds as Ultrafast and Effective Long‐Wavelength Phototriggers of 8Bromo‐Substituted Cyclic Nucleotides

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