Dendritic Voltage-gated Ion Channels Regulate the Action Potential Firing Mode of
Hippocampal CA1 Pyramidal Neurons. Jeffrey C. Magee and Michael Carruth. Neuroscience
Center, Louisiana State University Medical Center.
APStracts 6:0266N, 1999.
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 after-
hyperpolarization (AHP). Following localized application of 4-aminopyridine (4-AP) to the
distal apical dendritic arborization, the same current injections resulted in the generation of an
after-depolarization (ADP) and multiple action potentials. This burst firing was not observed
following localized application of 4-AP to the soma/proximal dendrites. The dendritic 4-
aminopyridine (4-AP) application allowed large amplitude Na+-dependent action potentials, that
were prolonged in duration, to backpropagate into the distal apical dendrites. No change in
action potential backpropagation was seen with proximal 4AP application. Both the ADP and
action potential bursting could be inhibited by the bath application of non-specific concentrations
of divalent Ca2+ channel blockers (NiCl and CdCl). Ca2+ 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) expressed even in the presence of high
concentrations of TTX (300-500 æM). 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 can then activate dendritic Ca2+ channels. While it appears that most Ca2+ channel subtypes
are important in burst generation, blockade of T- and R-type Ca2+ channels by NiCl (75 æM)
inhibited action potential bursting to a greater extent than L-channel (10 M nimodipine) or N-,
P/Q-type (1 M w-conotoxin MVIIC) Ca2+ channel blockade. This suggest that the Ni-sensitive
voltage-gated Ca2+ channels have the most important role in action potential burst generation. In
summary, these data suggest that the activation of dendritic voltage-gated Ca2+ channels, by large
amplitude backpropagating spikes, provides a prolonged inward current that is capable of
generating an after-depolarization (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.
Received 5 March 1999; accepted in final form 27 May 1999.
APS Manuscript Number J191-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiology Society.
Published in APStracts on 14 June 1999