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Volume 17, Number 12,
Issue of June 15, 1997
pp. 4517-4526
Copyright ©1997 Society for Neuroscience
Resurgent Sodium Current and Action Potential Formation in
Dissociated Cerebellar Purkinje Neurons
Received Jan. 30, 1997; revised March 22, 1997; accepted March 27, 1997.
Indira M. Raman and
Bruce
P. Bean
Vollum Institute, Oregon Health Sciences University, Portland,
Oregon 97201, and Department of Neurobiology, Harvard Medical School,
Boston, Massachusetts 02115
Voltage-dependent sodium channels were studied in dissociated
cerebellar Purkinje neurons from rats. In whole-cell recordings, a
tetrodotoxin (TTX)-sensitive inward
current was elicited when the membrane was repolarized to voltages
between 60 and 20 mV after depolarizations to +30 mV long enough to
produce maximal inactivation. At 40 mV, this "resurgent" current
peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on
average ~120 pA. CA3 pyramidal neurons had no such current. The
current may reflect recovery of inactivated channels through open
states, because in Purkinje neurons (but not CA3 neurons) there was
partial recovery from inactivation at 40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels
gave openings corresponding to resurgent and conventional transient
current. Action potentials were recorded from dissociated neurons under
current clamp to investigate the role of the resurgent current in
action potential formation. Purkinje neurons fired spontaneously at
~30 Hz. Hyperpolarization to 85 mV prevented spontaneous firing,
and brief depolarization then induced all-or-none firing of
conglomerate action potentials comprising three to four spikes. When
conglomerate action potentials were used as command voltages in
voltage-clamp experiments, TTX-sensitive sodium current was elicited
between spikes. The falling phase of an action potential is similar to
voltage patterns that activate resurgent sodium current, and thus,
resurgent sodium current likely contributes to the formation of
conglomerate action potentials in Purkinje neurons.
Key words:
sodium channel;
Purkinje neuron;
complex spike;
afterdepolarization;
tetrodotoxin;
pacemaking;
single channel;
action
potential;
cerebellum
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