Pflügers Archiv

, Volume 427, Issue 1–2, pp 71–79 | Cite as

Modulation of type A K+ current inDrosophila larval muscle by internal Ca2+; effects of the overexpression of frequenin

  • C. Poulain
  • A. Ferrús
  • A. Mallart
Excitable Tissues and Central Nervous Physiology


The calcium-dependent modulation of type A K+ current (IA) has been investigated using a two-electrode voltage clamp on larval muscle cells ofDrosophila. It was found that the amplitude ofIA increases when [Ca2+]0 is changed from 0.2 mM to 2 mM. The increase inIA amplitude is not due to overlap with the Ca2+-dependent fast K+ current,ICF, since it is observed also inslo1 mutants, which are deficient for this current. This effect is not due to Ca2+-dependent shifts in the steady-state activation/inactivation kinetics. The phenomenon is probably due to elevations in internal calcium since it is abolished by Ca2+ channel blockers and promoted by caffeine (5 mM) if added in the absence of external calcium. This calcium effect was dose-dependent since it was not observed in the presence caffeine plus 2 mM calcium in the bath nor for values of [Ca2+]0 above 4 mM. The Ca2+-dependent modulation ofIA is absent inV7, a mutation that causes overexpression of frequenin, a recoverin-like Ca2+-binding protein which stimulates guanylyl cyclase [31]. One possible explanation for the loss ofIA modulation in theV7 mutation is that the excess of frequenin alters intracellular cGMP-dependent metabolic pathways responsible for the internal calcium homeostasis.

Key words

Drosophila melanogaster Muscle A current Calcium Frequenin 


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  1. 1.
    Alkon D, Kubota M, Neary JT, Naito S, Coulter D, Rasmussen H (1986) C-kinase activation prolongs Ca2+-dependent inactivation of K+-currents. Biochem Biophys Res Commun 134:1215–1222Google Scholar
  2. 2.
    Alvarez-Leefmans FJ, Rink TJ, Tsien RY (1981) Free calcium ions in neurones ofHelix aspersa measured with ion-selective micro-electrodes. J Physiol (Lond) 315:531–548Google Scholar
  3. 3.
    Armstrong CM, Lopez-Barneo J (1987) External calcium ions are required for potassium channel gating in squid neurons. Science 236:712–714Google Scholar
  4. 4.
    Armstrong CM, Miller C (1990) Do voltage-dependent K+ channels require Ca2+? A critical test employing a heterologous expression system. Proc Natl Acad Sci USA 87:7579–7582Google Scholar
  5. 5.
    Belluzzi O, Sachi O, Wanke E (1985) A fast transient outward current in the rat sympathetic neurone studied under voltage clamp conditions. J Physiol (Lond) 358:91–108Google Scholar
  6. 6.
    Carignani C, Robello M, Marchetti C, Magas L (1991) A transient outward current dependent on external calcium in rat cerebellar granule cells. J Membr Biol 122:259–265Google Scholar
  7. 7.
    Chen QX, Wong RKS (1991) Intracellular Ca2+ suppressed a transient potassium current in hypocampal neurons. J Neurosci 11:337–343Google Scholar
  8. 8.
    Connor JA, Stevens CF (1971) Voltage-clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol (Lond) 213:21–30Google Scholar
  9. 9.
    Dizhoor AM, Ray S, Kumar S, Niemi G, Spencer M, Brolley D, Walsh KA, Philipov PP, Hurley JB, Stryer L (1991) Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase. Science 251:915–918Google Scholar
  10. 10.
    Dukes ID, Morad M (1991) The transient K+ current in rat ventricular myocytes: evaluation of its Ca2+ and Na+ dependence. J Physiol (Lond) 435:395–420Google Scholar
  11. 11.
    Elkins T, Ganetzky B, Wu, C-F (1986) ADrosophila mutation that eliminates a calcium-dependant potassium current. Proc Natl Acad Sci USA 83:8415–8419Google Scholar
  12. 12.
    Forsythe ID, Lindsell P, Stanfield PR (1992) Unitary A-currents of rat locus coeruleus grown in cell culture: rectification caused by internal Mg2+ and Na+. J Physiol (Lond) 451:553–583Google Scholar
  13. 13.
    Furukawa K-I, Ohshima N, Tawada-Iwata Y, Shigekawa M (1991) Cyclic GMP stimulates Na+/Ca2+ exchange in vascular smooth muscle cells in primary culture. J Biol Chem 266:12 337–12 341Google Scholar
  14. 14.
    Gho M, Mallart A (1986) Two distinct calcium-activated potassium currents in larval muscle fibresDrosophila melanogaster. Pflügers Arch 407:526–533Google Scholar
  15. 15.
    Green WN, Andersen OS (1991) Surface charges and ion channel function. Annu Rev Physiol 53:341–359Google Scholar
  16. 16.
    Hagiwara S, Takahashi K (1967) Surface density of calcium ions and calcium spikes in the barnacle fiber membrane. J Gen Physiol 50:583–601Google Scholar
  17. 17.
    Haugland FN, Wu C-F (1990) A voltage clamp analysis of gene-dosage effects of theShaker locus on larval potassium currents inDrosophila. J Neurosci 10:1357–1371Google Scholar
  18. 18.
    Jan YN, Jan LY (1976) Properties of the larval neuromuscular junction inDrosophila melanogaster. J Physiol (Lond) 262:189–214Google Scholar
  19. 19.
    Kawamura S (1993) Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin. Nature 362:855–857Google Scholar
  20. 20.
    Keicher E, Bilbaut A, Maggio K, Hernandez-Nicaise ML, Nicaise G (1991) The desheated periphery ofAplysia giant neuron. Fine structure and measurement of [Ca2+]o fluctuations with calcium-selective microelectrodes. Eur J Neuosci 3:10–17Google Scholar
  21. 21.
    Konishi M, Kurihara S (1987) Effects of caffeine on intracellular calcium concentration in frog skeletal muscle fibres. J Physiol (Lond) 383:269–283Google Scholar
  22. 22.
    Kostyuk PG, Martynyuk AE (1988) Potassium outward current dependent on extracellular calcium in snail neuronal membrane. Neuroscience 24:1081–1087Google Scholar
  23. 23.
    Lambrecht HG, Koch KW (1991) A 26 kd calcium binding protein from bovine rod outer segments as modulator of photoreceptor guanylate cylase. EMBO J 10:793–798Google Scholar
  24. 24.
    Lazarewicz JW, Kanje M, Sellström A, Hamberger A (1977) Calcium fluxes in cultured and bulk isolated neuronal and glial cells. J Neurochem 29:495–502Google Scholar
  25. 25.
    Mallart A, Angaut-Petit D, Bourret-Poulain C, Ferrús A (1991) Nerve terminal excitability and neuromuscular transmission in T(X; Y)V7 andShaker mutants ofDrosophila melanogaster. J Neurogenet 7:75–84Google Scholar
  26. 26.
    Mayer ML, Sugiyama K (1988) A modulatory action of divalent cations on transient outward current in cultured rat sensory neurones. J Physiol (Lond) 396:417–433Google Scholar
  27. 27.
    Moran O, Dascal N, Lotan I (1991) Modulation of aShaker A-channel by protein kinase C activation. FEBS Lett 279:256–260Google Scholar
  28. 28.
    Nachshen DA (1985) Regulation of cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. J Physiol (Lond) 363:87–101Google Scholar
  29. 29.
    Nicholson C, Ten Bruggencate G, Steinberg R, Stöckle H (1977) Calcium modulation in rat brain extracellular microenvironment demonstrated with ion-selective micropipette. Proc Natl Acad Sci USA 74:1287–1290Google Scholar
  30. 30.
    Pardo LA, Heinemann SH, Terlau H, Ludewig U, Lorra C, Pongs O, Stühmer W (1992) Extracellular K+ modulates a rat brain K+ channel. Proc Natl Acad Sci USA 89:2466–2470Google Scholar
  31. 31.
    Pongs O, Lindemeier J, Zhu XR, Theil T, Engelkamp D, Krah-Jentgens I, Lambrecht HG, Koch KW, Schwemer J, Rivosecchi R, Mallart A, Galcerán J, Canal I, Barbas JA, Ferrús A (1993) Frequenin — a novel calcium binding protein that modulates synaptic efficacy in theDrosophila nervous system. Neuron 11:15–28Google Scholar
  32. 32.
    Przywara DA, Bhave SV, Bhave A, Chowdhury PS, Wakade TD, Wakade AR (1992) Activation of K+ channels by lanthanum contributes to the block of transmitter release in chick and rat sympathetic neurons. J Membr Biol 125:155–162Google Scholar
  33. 33.
    Rehm H, Pelzer S, Cochet C, Chambaz E, Tempel BL, Trautwein W, Pelzer D, Lazdunski M (1989) Dendrotoxin-binding brain membrane protein displays a K+ channel activity that is stimulated by both cAMP-dependant and endogenous phosphorylations. Biochemistry 28:6455–6460Google Scholar
  34. 34.
    Rivosecchi R, Pongs O, Theil T, Mallart A (1994) Implication of frequenin in the facilitation of transmitter release inDrosophila. J Physiol (Lond) 474:223–232Google Scholar
  35. 35.
    Rudy B (1988) Diversity and ubiquity of K channels. Neuroscience 25:729–749Google Scholar
  36. 36.
    Salkoff LB, Wyman RJ (1983) Ion currents inDrosophila flight muscles. J Physiol (Lond) 337:687–709Google Scholar
  37. 37.
    Sellström A, Henn F, Jacobson I, Venema R (1981) On the Ca2+-permeability of neurons and glia. Acta Physiol Scand 113:253–258Google Scholar
  38. 38.
    Shearman MS, Sekiguchi K, Nishizuka Y (1989) Modulation of ion channel activity: a key function of the protein kinase C enzyme family. Pharmacol Revs 41:211–237Google Scholar
  39. 39.
    Shimahara T (1983) Presynaptic modulation of transmitter release by the early outward potassium current inAplysia. Brain Res 263:51–56Google Scholar
  40. 40.
    Singh S, Wu C-F (1989) Complete separation of four potassium currents inDrosophila. Neuron 2:1325–1329Google Scholar
  41. 41.
    Singh S, Wu C-F (1990) Properties of potassium currents and their role in membrane excitability inDrosophila larval muscle fibers. J Exp Biol 152:59–76Google Scholar
  42. 42.
    Strong JA (1984) Modulation of potassium current kinetics in bag cell neurons ofAplysia by an activator of adenylate cyclase. J Neurosci 4:2772–2783Google Scholar
  43. 43.
    Tanouye MA, Ferrús A, Fujita SC (1981) Abnormal action potentials associated with theShaker complex locus ofDrosophila. Proc Natl Acad Sci USA 78:6548–6552Google Scholar
  44. 44.
    Wu C-F, Haugland FN (1985) Voltage-clamp analysis of membrane currents in larval muscle fibers ofDrosophila: alteration of potassium currents inShaker mutants. J Neurosci 5:2626–2640Google Scholar
  45. 45.
    Yamagata K, Goto K, Kuo C-H, Kondo H, Miki N (1990) Visinin: a novel calcium binding protein expressed in retinal cone cells. Neuron 2:469–476Google Scholar
  46. 46.
    Zhong Y, Wu C-F (1991) Alteration of four identified K+ currents inDrosophila muscle by mutations ineag. Science 252:1562–1564Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • C. Poulain
    • 1
  • A. Ferrús
    • 1
  • A. Mallart
    • 1
  1. 1.Unité de Physiologie Neuromusculaire, Laboratoire de Neurobiologie Cellulaire et MoléculaireCNRSGif-sur-YvetteFrance

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