title: Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons.
abstract: The role of dendritic voltage-gated ion channels in the generation of action potential bursting was investigated using whole cell patch-clamp recordings from the soma and dendrites of CA1 pyramidal neurons located in hippocampal slices of adult rats. Under control conditions somatic current injections evoked single action potentials that were associated with an afterhyperpolarization (AHP). After localized application of 4-aminopyridine (4-AP) to the distal apical dendritic arborization, the same current injections resulted in the generation of an afterdepolarization (ADP) and multiple action potentials. This burst firing was not observed after localized application of 4-AP to the soma/proximal dendrites. The dendritic 4-AP application allowed large-amplitude Na(+)-dependent action potentials, which were prolonged in duration, to backpropagate into the distal apical dendrites. No change in action potential backpropagation was seen with proximal 4-AP application. Both the ADP and action potential bursting could be inhibited by the bath application of nonspecific concentrations of divalent Ca(2+) channel blockers (NiCl and CdCl). Ca(2+) channel blockade also reduced the dendritic action potential duration without significantly affecting spike amplitude. Low concentrations of TTX (10-50 nM) also reduced the ability of the CA1 neurons to fire in the busting mode. This effect was found to be the result of an inhibition of backpropagating dendritic action potentials and could be overcome through the coordinated injection of transient, large-amplitude depolarizing current into the dendrite. Dendritic current injections were able to restore the burst firing mode (represented as a large ADP) even in the presence of high concentrations of TTX (300-500 microM). These data suggest the role of dendritic Na(+) channels in bursting is to allow somatic/axonal action potentials to backpropagate into the dendrites where they then activate dendritic Ca(2+) channels. Although it appears that most Ca(2+) channel subtypes are important in burst generation, blockade of T- and R-type Ca(2+) channels by NiCl (75 microM) inhibited action potential bursting to a greater extent than L-channel (10 microM nimodipine) or N-, P/Q-type (1 microM omega-conotoxin MVIIC) Ca(2+) channel blockade. This suggest that the Ni-sensitive voltage-gated Ca(2+) channels have the most important role in action potential burst generation. In summary, these data suggest that the activation of dendritic voltage-gated Ca(2+) channels, by large-amplitude backpropagating spikes, provides a prolonged inward current that is capable of generating an ADP and burst of multiple action potentials in the soma of CA1 pyramidal neurons. Dendritic voltage-gated ion channels profoundly regulate the processing and storage of incoming information in CA1 pyramidal neurons by modulating the action potential firing mode from single spiking to burst firing.
authors.affiliation: Neuroscience Center, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Magee
authors.forename: M
authors.initials: M
authors.lastname: Carruth
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013779:Tetrodotoxin; C022838:nickel chloride; D009532:Nickel; D015761:4-Aminopyridine; D019256:Cadmium Chloride