Extracellular calcium sensed by a novel cation channel in hippocampal neurons.

Extracellular concentrations of Ca2+ change rapidly and transiently in the brain during excitatory synaptic activity. To test whether such changes in Ca2+ can play a signaling role we examined the effects of rapidly lowering Ca2+ on the excitability of acutely isolated CA1 and cultured hippocampal neurons. Reducing Ca2+ excited and depolarized neurons by activating a previously undescribed nonselective cation channel. This channel had a single-channel conductance of 36 pS, and its frequency of opening was inversely proportional to the concentration of Ca2+. The inhibition of gating of this channel was sensitive to ionic strength but independent of membrane potential. The ability of this channel to sense Ca2+ provides a novel mechanism whereby neurons can respond to alterations in the extracellular concentration of this key signaling ion.

[1]  H. Qian,et al.  Evidence for hemi‐gap junctional channels in isolated horizontal cells of the skate retina , 1993, Journal of neuroscience research.

[2]  M. Hediger,et al.  Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid , 1993, Nature.

[3]  F. Sachs,et al.  Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions. , 1989, Science.

[4]  R. Miledi,et al.  A monovalent cationic conductance that is blocked by extracellular divalent cations in Xenopus oocytes. , 1995, The Journal of physiology.

[5]  L. Vyklický Calcium‐mediated modulation of N‐methyl‐D‐aspartate (NMDA) responses in cultured rat hippocampal neurones. , 1993, The Journal of physiology.

[6]  R. MacKinnon,et al.  Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel , 1993, Neuron.

[7]  S. Snyder,et al.  Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Tsien,et al.  Mechanism of ion permeation through calcium channels , 1984, Nature.

[9]  W. Bönigk,et al.  Structural Features of Cyclic Nucleotide-Gated Channels , 1993 .

[10]  M. Mayer,et al.  Multiple effects of spermine on N‐methyl‐D‐aspartic acid receptor responses of rat cultured hippocampal neurones. , 1993, The Journal of physiology.

[11]  I. Módy,et al.  Regulation of N‐methyl‐D‐aspartate receptors revealed by intracellular dialysis of murine neurones in culture. , 1989, The Journal of physiology.

[12]  J. López-Barneo,et al.  External calcium ions are required for potassium channel gating in squid neurons. , 1987, Science.

[13]  B. Hille Ionic channels of excitable membranes , 2001 .

[14]  C. Zorumski,et al.  The effect of agonist concentration, membrane voltage and calcium on n-methyl-d-aspartate receptor desensitization , 1990, Neuroscience.

[15]  U. Heinemann,et al.  Step reductions in extracellular Ca2+ activate a transient inward current in chick dorsal root ganglion cells. , 1986, Biophysical journal.

[16]  K. Krnjević,et al.  Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus. , 1982, Canadian journal of physiology and pharmacology.

[17]  U. Heinemann,et al.  Activity-dependent ionic changes and neuronal plasticity in rat hippocampus. , 1990, Progress in brain research.

[18]  R. Huganir,et al.  Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit , 1996, Cell.

[19]  J. Lerma,et al.  Chloride transport blockers prevent N-methyl-D-aspartate receptor-channel complex activation. , 1992, Molecular pharmacology.

[20]  I. Módy,et al.  Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. , 1987, Journal of neurophysiology.

[21]  H. Haas,et al.  Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission , 1982, Nature.

[22]  C. Armstrong,et al.  Do voltage-dependent K+ channels require Ca2+? A critical test employing a heterologous expression system. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Christian Rosenmund,et al.  Rundown of N‐methyl‐D‐aspartate channels during whole‐cell recording in rat hippocampal neurons: role of Ca2+ and ATP. , 1993, The Journal of physiology.

[24]  W. Almers,et al.  Non‐selective conductance in calcium channels of frog muscle: calcium selectivity in a single‐file pore. , 1984, The Journal of physiology.

[25]  S. Jones,et al.  Surface charge and calcium channel saturation in bullfrog sympathetic neurons , 1995, The Journal of general physiology.

[26]  J. Lerma Spermine regulates N-methyl-d-aspartate receptor desensitization , 1992, Neuron.

[27]  H. Sackin Review of Mechanosensitive Channels , 1995 .

[28]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[29]  Uwe Heinemann,et al.  Effects of NMDA antagonists on picrotoxin-, low Mg2+- and low Ca2+-induced epileptogenesis and on evoked changes in extracellular Na+ and Ca2+ concentrations in rat hippocampal slices , 1989, Epilepsy Research.

[30]  E. A. Schwartz,et al.  Hemi‐gap‐junction channels in solitary horizontal cells of the catfish retina. , 1992, The Journal of physiology.

[31]  D. W. McBride,et al.  Structure‐activity relations of amiloride and its analogues in blocking the mechanosensitive channel in Xenopus oocytes , 1992, British journal of pharmacology.

[32]  Stephan Frings,et al.  Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels , 1995, Neuron.

[33]  Christian Rosenmund,et al.  Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  Christopher Miller,et al.  Ionic channels of excitable membranes. Second edition By Bertil Hille. Sunderland, Massachusetts: Sinauer. (1991). 607 pp. $46.95 , 1992, Cell.

[35]  R. Tsien,et al.  Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions , 1995, Neuron.