Extracellular calcium modulates persistent sodium current-dependent burst-firing in hippocampal pyramidal neurons

J Neurosci. 2001 Jun 15;21(12):4173-82. doi: 10.1523/JNEUROSCI.21-12-04173.2001.

Abstract

The generation of high-frequency spike bursts ("complex spikes"), either spontaneously or in response to depolarizing stimuli applied to the soma, is a notable feature in intracellular recordings from hippocampal CA1 pyramidal cells (PCs) in vivo. There is compelling evidence that the bursts are intrinsically generated by summation of large spike afterdepolarizations (ADPs). Using intracellular recordings in adult rat hippocampal slices, we show that intrinsic burst-firing in CA1 PCs is strongly dependent on the extracellular concentration of Ca(2+) ([Ca(2+)](o)). Thus, lowering [Ca(2+)](o) (by equimolar substitution with Mn(2+) or Mg(2+)) induced intrinsic bursting in nonbursters, whereas raising [Ca(2+)](o) suppressed intrinsic bursting in native bursters. The induction of intrinsic bursting by low [Ca(2+)](o) was associated with enlargement of the spike ADP. Low [Ca(2+)](o)-induced intrinsic bursts and their underlying ADPs were suppressed by drugs that reduce the persistent Na(+) current (I(NaP)), indicating that this current mediates the slow burst depolarization. Blocking Ca(2+)-activated K(+) currents with extracellular Ni(2+) or intracellular chelation of Ca(2+) did not induce intrinsic bursting. This and other evidence suggest that lowering [Ca(2+)](o) may induce intrinsic bursting by augmenting I(NaP). Because repetitive neuronal activity in the hippocampus is associated with marked decreases in [Ca(2+)](o), the regulation of intrinsic bursting by extracellular Ca(2+) may provide a mechanism for preferential recruitment of this firing mode during certain forms of hippocampal activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Chelating Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enzyme Activators / pharmacology
  • Extracellular Space / metabolism
  • Gap Junctions / drug effects
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Lysine / analogs & derivatives
  • Nickel / pharmacology
  • Phenytoin / pharmacology
  • Phorbol Esters / pharmacology
  • Potassium Channel Blockers
  • Potassium Channels / metabolism
  • Protein Kinase C / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Rats
  • Sensory Thresholds / physiology
  • Sodium / metabolism
  • Sodium Channel Blockers
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology

Substances

  • Chelating Agents
  • Enzyme Activators
  • Phorbol Esters
  • Potassium Channel Blockers
  • Potassium Channels
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin
  • Egtazic Acid
  • Phenytoin
  • Nickel
  • Sodium
  • Protein Kinase C
  • biocytin
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Lysine
  • Calcium