Selective inhibition of the phospholipase C pathway blocks one light-activated current component in Limulus photoreceptor

Zeitschrift für vergleichende Physiologie - Tập 177 - Trang 601-610 - 1995
K. Contzen1, K. -H. Richter1, K. Nagy1
1Institut für Biologie II, RWTH Aachen, Aachen, Germany

Tóm tắt

Light-activated receptor currents were measured in Limulus ventral nerve photoreceptors by a two electrode voltage clamp. Short flashes stimulate three different current components (C1, C2, C3). Currents were measured before and after injection of neomycin, heparin and BAPTA. These substances inhibit the inositol phosphate pathway at different stages. Each substance selectively blocked the C2 component. After the block of C2 the other two components could be further stimulated, but their amplitudes were usually reduced. High concentrations of BAPTA, however, increased the amplitude (two-fold) and decay time constant (eight-fold) of C1, suggesting that calcium is necessary for the deactivation of the C1 current. The time to maximum for C2 is known to be dependent on the light-adaptation state and the stimulus intensity. It is shown here that the time to the maximum of C2 remains nearly unchanged when C2 is gradually inhibited by BAPTA, but is prolonged when C2 is inhibited by neomycin. Since the kinetics of an enzyme reaction depend on the substrate concentration, these results indicate, as expected, that neomycin changes the substrate concentration and thus changes the rate and gain of the cascade, while BAPTA changes the product concentration, i.e. binds the released calcium. Therefore, these observations support the hypothesis that the negative feedback of adaptation regulates the phospholipase C cascade at the same early stage, where the neomycin acts. The same consideration suggests that after the calcium release no further amplification occurs in the transduction cascade since the time to maximum with BAPTA remains unchanged. The results are explained by three parallel transduction pathways. It is suggested that the inositol phosphate cycle regulates the gain of the other two pathways by the release of calcium ions.

Tài liệu tham khảo

Aldrich RW, Corey DP, Stevens CF (1983) A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 301: 436–441 Bacigalupo J, Johnson EC, Vergara C, Lisman JE (1991) Lightdependent channels from excised patches of Limulus ventral nerve photoreceptors are opened by cGMP. Proc Natl Acad Sci USA 88: 7938–7942 Bolsover SR, Brown JE (1985) Calcium ion, an intracellular messenger of light adaptation, also participates in excitation of Limulus photoreceptors. J Physiol (Lond) 364: 381–393 Brown JE, Rubin LJ, Ghalayini AJ, Tarver AP, Irvine RF, Berridge MJ, Anderson RE (1984) Myo-inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors. Nature 311: 160–163 Corson DW, Fein A (1983) Quantitative pressure injection of picoliter volumes into Limulus ventral photoreceptors. Biophys J 44: 299–304 Deckert A (1991) Experimental and theoretical investigations of the calcium regulation in Limulus ventral nerve photoreceptors. Doct Thesis, RWTH Aachen Deckert A, Stieve H (1990) Electrogenic Na+/Ca2+ exchanger, the calcium link between intra- and extracellular space in the Limulus ventral nerve photoreceptor. J Physiol (Lond) 433: 467–482 Deckert A, Nagy K, Helrich CS, Stieve H (1992) Three components in the light-induced current of the Limulus ventral photoreceptor. J Physiol (Lond) 453: 69–96 Faddis MN, Brown JE (1993) Intracellular injection of heparin and polyamines. Effects on phototransduction in Limulus ventral photoreceptors. J Gen Physiol 101: 909–931 Fain GL, Lisman JE (1981) Membrane conductances of photoreceptors. Progr Biophys Mol Biol 37: 91–147 Fein A, Payne R (1989) Phototransduction in Limulus photoreceptors: Roles of calcium and inositol trisphosphate. In: Stavenga DG, Hardie RC (eds) Facets of vision. Springer, Berlin Heidelberg New York, pp 173–185 Fein A, Payne R, Corson DW, Berridge MJ, Irvine RF (1984) Photoreceptor excitation and adaptation by inositol 1,4,5-trisphosphate. Nature 311: 157–160 Feng JJ, Frank TM, Fein A (1991) Excitation of Limulus photoreceptors by cGMP. Biophys J 59:531a Frank TM, Fein A (1991) The role of the inositol phosphate cascade in visual excitation of invertebrate microvillar photoreceptors. J Gen Physiol 97: 697–723 Hardie RC, Minke B (1992) The trp gene is essential for a lightactivated Ca2+ channel in Drosophila photoreceptors. Neuron 8: 643–651 Hardie RC, Minke B (1993) Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implication for phosphoinositide-mediated Ca2+ mobilization. Trends Neurosci 16: 371–376 Hardie RC, Minke B (1994) Calcium-dependent inactivation of light-sensitive channels in Drosophila photoreceptors. J Gen Physiol 103: 409–427 Haynes LW (1992) Block of the cyclic GMP-gated channel of vertebrate rod and cone photoreceptors by l-cis-diltiazem. J Gen Physiol 100: 783–801 Johnson EC, Robinson PR, Lisman JE (1986) Cyclic GMP is involved in the excitation of invertebrate photoreceptors. Nature 324: 468–470 Lisman JE, Brown JE (1971) Two light-induced processes in the photoreceptor cells of Limulus ventral eye. J Gen Physiol 58: 544–561 Maaz G, Nagy K, Stieve H, Klomfaß J (1981) The electrical light response of the Limulus ventral nerve photoreceptor, a superposition of distinct components — observable by variation of the state of light adaptation. J Comp Physiol 141: 303–310 Marton LJ, Morris DR (1987) Molecular and cellular functions of the polyamines. In: McCann PP, Pegg AE, Sjoerdsma A (eds) Inhibition of polyamine metabolism. Academic Press, New York, pp 79–105 Nagy K (1990) Kinetic properties of single ion channels activated by light in Limulus ventral nerve photoreceptors. Eur Biophys J 19: 47–54 Nagy K (1991) Biophysical processes in invertebrate photoreceptors: recent progress and a critical overview based on Limulus photoreceptors. Q Rev Biophys 24: 165–226 Nagy K (1992) Non-independent quantum bumps in Limulus ventral nerve photoreceptors — a new insight in the light transduction mechanism. Neurosci Lett 144: 99–102 Nagy K (1993) Cyclic nucleotides and inositol trisphosphate activate distinct components of the receptor current in Limulus ventral nerve photoreceptors. Neurosci Lett 152: 1–4 Nagy K (1994) Inhibition of the first component of the receptor current in Limulus photoreceptor. Neuroreport 5: 847–849 Nagy K, Stieve H (1990) Light-activated single channel currents in Limulus ventral photoreceptors. Eur Biophys J 18: 221–224 Nagy K, Contzen K, Stieve H (1993) Two components of the receptor current are developed from distinct elementary signals in Limulus ventral nerve photoreceptor. Eur Biophys J 22: 341–350 Nasi E (1991) Two light-dependent conductances in Lima rhabdomeric photoreceptors. J Gen Physiol 97: 55–72 Nasi E, Gomez MP (1992) Light-activated ion channels in solitary photoreceptors of the scallop Pecten irradians. J Gen Physiol 99: 747–769 O'Day PM, Gray-Keller MP (1989) Evidence for electrogenic Na+/Ca2+ exchange in Limulus ventral photoreceptors. J Gen Physiol 93: 473–492 Payne R, Fein A (1986) The initial response of Limulus ventral photoreceptors to bright flashes. Released calcium as a synergist to excitation. J Gen Physiol 87: 243–269 Payne R, Corson DW, Fein A (1986a) Pressure injection of calcium both excites and adapts Limulus ventral photoreceptors. J Gen Physiol 88: 107–126 Payne R, Corson DW, Fein A, Berridge MJ (1986b) Excitation and adaptation of Limulus ventral nerve photoreceptors by inositol 1,4,5 trisphosphate result from a rise in intracellular calcium. J Gen Physiol 88: 127–142 Payne R, Walz B, Levy S, Fein A (1988) The localization of calcium release by inositol trisphosphate in Limulus photoreceptors and its control by negative feedback. Phil Trans R Soc Lond B 320: 359–379 Payne R, Flores MF, Fein A (1990) Feedback inhibition by calcium limits the release of calcium by inositol trisphosphate in Limulus ventral photoreceptors. Neuron 4: 547–555 Robinson PR, Wood SF, Szuts EZ, Fein A, Hamm HE, Lisman JE (1990) Light-dependent GTP-binding proteins in squid photoreceptors. Biochem J 272: 79–85 Shin J, Richard EA, Lisman JE (1993) Ca2+ is an obligatory intermediate in the excitation cascade of Limulus photoreceptors. Neuron 11: 845–855 Stern JH, Kaupp UB, MacLeish PR (1986) Control of the light-regulated current in rod photoreceptors by cyclic GMP, calcium and l-cis-diltiazem. Proc Natl Acad Sci USA 83: 1163–1167 Stieve H, Niemeyer B, Aktories K, Hamm HE (1992) Disturbing GTP-binding protein function through microinjection into the visual cell of Limulus. Z Naturforsch 47c: 915–921 Tsuda M, Tsuda T (1990) Two distinct light regulated G-proteins in octopus photoreceptors. Biochim Biophys Acta 1052: 204–210 Tsuda M, Kikkawa S, Iwasa T, Nakagawa M (1994) Multiple G proteins coupled with illuminated rhodopsin in octopus photoreceptors. Sixth International Conference on Retinal Proteins, Leiden, Abstract 162