Abstract
The contribution of L-, N-, P- and Q-type Ca2+ channels to excitatory and inhibitory synaptic transmission and to whole-cell Ba2+ currents through Ca2+ channels (Ba2+ currents) was investigated in rat hypothalamic neurons grown in dissociated cell culture. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) were evoked by stimulating individual neurons under whole-cell patch-clamp conditions. The different types of high-voltage-activated (HVA) Ca2+ channels were identified using nifedipine, ω -Conus geographus toxin VIA (ω-CTx GVIA), ω -Agelenopsis aperta toxin IVA (ω-Aga IVA), and ω -Conus magus toxin VIIC (ω-CTx MVIIC). N-, but not P- or Q-type Ca2+ channels contributed to excitatory as well as inhibitory synaptic transmission together with Ca2+ channels resistant to the aforementioned Ca2+ channel blockers (resistant Ca2+ channels). Reduction of postsynaptic current (PSC) amplitudes by N-type Ca2+ channel blockers was significantly stronger for IPSCs than for EPSCs. In most neurons whole-cell Ba2+ currents were carried by L-type Ca2+ channels and by at least two other Ca2+ channel types, one of which is probably of the Q-type and the others are resistant Ca2+ channels. These results indicate a different contribution of the various Ca2+ channel types to excitatory and inhibitory synaptic transmission and to whole-cell currents in these neurons and suggest different functional roles for the distinct Ca2+ channel types.
Similar content being viewed by others
References
Ahlijanian MK, Westenbroek RE, Catterall WA (1990) Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina. Neuron 4:819–832
Aosaki T, Kasai H (1989) Characterization of two kinds of high-voltage activated Ca-channel currents in chick sensory neurons. Pflügers Arch 414:150–156
Artalejo CR, Adams ME, Fox AP (1994) Three types of Ca2+ channels trigger secretion with different efficacies in chromaffin cells. Nature 367:72–76
Augustine GJ, Charlton MP, Smith SJ (1987) Calcium action in synaptic transmitter release. Annu Rev Neurosci 10:633–693
Bargas J, Howe A, Eberwine J, Cao Y, Surmeier DJ (1994) Cellular and molecular characterization of Ca2+ currents in acutely isolated, adult rat neostriatal neurons. J Neurosci 14:6667–6686
Basarsky TA, Parpura V, Haydon PG (1994) Hippocampal synaptogenesis in cell culture: developmental time course of synapse formation, calcium influx, and synaptic protein distribution. J Neurosci 14:6402–6411
Bean BP (1984) Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci USA 81:6388–6392
Bennett MK, Calakos N, Serieller RH (1992) Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257:255–259
Birnbaumer L, Campbell KP, Catterall WA, Harpold MM, Hofmann F, Horne WA, Mori Y, Schwartz A, Snutch TP, Tanabe T, Tsien RW (1994) The naming of voltage-gated calcium channels. Neuron 13:505–506
Boland LM, Morrill JA, Bean B (1994) w-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons. J Neurosci 14:5011–5027
Carbone E, Lux HD (1987) Kinetics and selectivity of a low- voltage-activated calcium current in chick and rat sensory neurones. J Physiol (Lond) 386:547–570
Dunlap K, Luebke JI, Turner TJ (1995) Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci 18:89–98
Dutar P, Rascol O, Lamour Y (1989) w-Conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus. Eur J Pharmacol 174:261–266
Edmonds B, Klein M, Dale N, Kandel ER (1990) Contributions of two types of calcium channels to synaptic transmission and plasticity. Science 250:1142–1147
Eilers J, Augustine GJ, Konnerth A (1995) Subthreshold synaptic Ca2+ signalling in fine dendrites and spines of cerebellar Purkinje neurons. Nature 373:155–158
Grantham CJ, Bowman D, Bath CP, Bell DC, Bleakman D (1994) w-conotoxin MVIIC reversibly inhibits a human N-type calcium channel and calcium influx into chick synaptosomes. Neuropharmacology 33:255–258
Hell JW, Westenbroek RE, Warner C, Ahlijanian MK, Prystay W, Gilbert MM, Snutch TP, Catterall WA (1993) Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J Cell Biol 123:949–962
Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, Mcintosh JM, Cruz LJ, Imperial SJ, Olivera BM (1992) A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron 9:69–77
Horne AL, Kemp JA (1991) The effect of w-conotoxin GVIA on synaptic transmission within the nucleus accumbens and hippocampus of the rat in vitro. Br J Pharmacol 103:1733–1739
Johnston D, Sakmann B, Ross WN, Catterall WA (1994) Symposium. New approaches to understanding dendrites. Soc Neurosci Abstr 20:427
Jonas P, Major G, Sakmann B (1993) Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of the rat hippocampus. J Physiol (Lond) 472:615–663
Kamiya H, Sawada S, Yamamoto C (1988) Synthetic w-conotoxin blocks synaptic transmission in the hippocampus in vitro. Neurosci Lett 91:84–88
Kasai H, Neher E (1992) Dihydropyridine-sensitive and ω- conotoxin-sensitive calcium channels in a mammalian neuro- blastoma-glioma cell line. J Physiol (Lond) 448:161–188
Kasai H, Aosaki T, Fukuda J (1987) Presynaptic Ca-antago- nist omega-conotoxin irreversibly bocks N-type Ca-channels in chick sensory neurons. Neurosci Res 4:228–235
Katz B (1969) The release of neural transmitter substances. Liverpool University Press, Liverpool
Lévêque C, El Far O, Martin-Moutot N, Sato K, Kato R, Takahashi M, Seagar MJ (1994) Purification of the N-type calcium channel associated with syntaxin and synaptotagmin. A complex implicated in synaptic vesicle exocytosis. J Biol Chem 269:6306–6312
Liévano A, Bolden A, Horn R (1994) Calcium channels in excitable cells: divergent genotypic and phenotypic expression of αl-subunits. Am J Physiol 267:C411-C424
Lovinger DM, Merritt A, Reyes D (1994) Involvement of N- and non-N-type calcium channels in synaptic transmission at corticostriatal synapses. Neuroscience 62:31–40
Luebke JI, Dunlap K, Turner TJ (1993) Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron 11:895–902
Magee JC, Johnston D (1995) Synaptic activation of voltage- gated channels in the dendrites of hippocampal pyramidal neurons. Science 268:301–304
Markram H, Sakmann B (1994) Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc Natl Acad Sei USA 24:5207–5211
McCleskey EW, Fox AP, Feldman DH, Cruz LJ, Olivera BM, Tsien RW, Yoshikami D (1987) co-Conotoxin: direct and persistent blockade of specific types of calcium channels in neuron but not muscle. Proc Natl Acad Sci USA 84:4327–4331
Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME (1992) P-type calcium channels blocked by the spider toxin ω-Aga-IVA. Nature 355:827–829
Müller TH, Misgeld U, Swandulla D (1992) Ionic currents in rat hypothalamic neurones. J Physiol (Lond) 450:341–362
Müller W, Swandulla D (1995) Synaptic feedback excitation has hypothalamic neural networks generate quasirhythmic burst activity. J Neurophysiol 73:855–861
O’Connor VM, Shamotienko O, Grishin E, Betz H (1993) On the structure of the “synaptosecretosome”: evidence for a neurexin/synaptotagmin/syntaxin/Ca2+ channel complex. FEBS Lett 326:255–261
Olivera BM, Gray WR, Zeikus R, Mcintosh JM, Varga J, Rivier J, deSantos V, Cruz LJ (1985) Peptide neurotoxins from fish-hunting cone snails. Science 230:1338–1343
Perez-Reyes E, Schneider T (1994) Calcium channels: structure, function, and classification. Drug Dev Res 33:295–318
Perez-Reyes E, Wei XY, Castellano A, Birnbaumer L (1990) Molecular diversity of L-type calcium channels. J Biol Chem 265:20430–20436
Pfrieger FW, Veselowsky NS, Gottmann K, Lux HD (1992) Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro. J Neurosci 12:4347–4357
Polio A, Lovallo M, Biancardi E, Sher E, Socci C, Carbone E (1993) Sensitivity to dihydropyridines, co-conotoxin and nor- adrenaline reveals multiple high-voltage-activated Ca2+ channels in rat insulinoma human pancreatic ß-cells. Pflügers Arch 423:462–471
Randall A, Tsien RW (1995) Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule cells. J Neurosci 15:2995–3012
Saccomano NA, Ahlijanian MK (1994) Ca2+ channel toxins: tools to study channel structure and function. Drug Dev Res 33:319–343
Sather WA, Tanabe T, Zhang JF, Mori Y, Adams ME, Tsien RW (1993) Distinctive biophysical and pharmacological properties of class A (BI) calcium channel αl subunits. Neuron 11:291–303
Sheng Z-H, Rettig J, Takahashi M, Catterall WA (1994) Identification of a syntaxin-binding site on N-type calcium channels. Neuron 13:1303–1313
Snutch TP, Leonard JP, Gilbert MM, Lester HA, Davidson N (1990) Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sei USA 87:3391–3395
Spruston N, Schiller Y, Stuart G, Sakmann B (1995). Activity- dependent action potential invasion and calcium influx into hip- pocampal CA 1 dendrites. Science 268:297–300
Stea A, Tomlinson WJ, Soon TW, Bourinet E, Dubel SJ, Vincent SR, Snutch TP (1994) Localisation and functional properties of a rat brain α 1A calcium channel reflect similarities to neuronal Q- and P-type channels. Proc Natl Acad Sei USA 91:10576–10580
Stuart GJ, Sakmann B (1994) Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367:69–72
Swandulla D, Misgeld U (1990) Development and properties of synaptic mechanisms in a network of rat hypothalamic neurons grown in culture. J Neurophysiol 64:715–726
Swandulla D, Misgeld U, Beckh S (1993) Molecular properties of the glutamate receptor mediating synaptic excitation in rat hypothalamic neurons. Neurosci Lett 159:59–63
Takahashi T, Momiyama A (1993) Different types of calcium channels mediate central synaptic transmission. Nature 366: 156–158
Turner TJ, Adams ME, Dunlap K (1992) Calcium channels coupled to glutamate release identified by w-Aga-IVA. Science 258:310–313
Turner TJ, Lampe RA, Dunlap K (1995) Characterization of presynaptic calcium channels with cu-conotoxin MVIIC and w- grammotoxin SI A: role for a resistant calcium channel type in neurosecretion. Mol Pharmacol 47:348–353
Wheeler DB, Randall A, Tsien RW (1994) Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission. Science 264:107–111
Williams ME, Feldmann DH, Mc Cue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM (1992) Structure and functional expression of α1,, α2, and ß subunits of a novel human neuronal calcium channel subtype. Neuron 8:71–84
Wu L-G, Saggau P (1994) Pharmacological identification of two types of presynaptic voltage-dependent calcium channels at CA3-CA1 synapses of the hippocampus. J Neurosci 14:5613–5622
Yawo H, Chuhma N (1994) w-Conotoxin-sensitive and -resistant transmitter release from the chick ciliary presynaptic terminal. J Physiol (Lond) 477:437–448
Yoshida A, Oho C, Omori A, Kuwahara R, Ito T, Takahashi M (1992) HPC-1 is associated with synaptotagmin and w-cono- toxin receptor. J Biol Chem 267:24925–24928
Yoshikami D, Bagabaldo Z, Olivera BM (1989) The inhibitory effects of omega-conotoxins on Ca channels and synapses. Ann NY Acad Sci 560:230–248
Zhang J-F, Randall AD, Ellinor PT, Home WA, Sather WA, Tanabe T, Schwarz TL, Tsien RW (1993) Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuro- pharmacology 32:1075–1088
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zeilhofer, H.U., Müller, T.H. & Swandulla, D. Calcium channel types contributing to excitatory and inhibitory synaptic transmission between individual hypothalamic neurons. Pflugers Arch. 432, 248–257 (1996). https://doi.org/10.1007/s004240050131
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s004240050131