Properties of calcium spikes revealed during GABAA receptor antagonism in
hippocampal CA1 neurons from guinea pigs.
Masami Miura, Masatomo Yoshioka, Hiroyoshi Miyakawa, Hiroshi Kato and Ken-Ichi
Ito.
From.
APStracts 4:157N, 1997.
ABSTRACT
Intracellular electrical responses and changes in intracellular calcium
concentration ([Ca2+]i) in response to activation of synaptic inputs and to
direct current injections were recorded simultaneously from CA1 pyramidal
neurons (n = 42) in guinea-pig hippocampal slices. In the presence of the
GABAA receptor antagonists, bicuculline (25 M) and picrotoxin (10 M), broad (>
20 ms) all-or-none spikes were induced by activation of synaptic inputs (20
pulses, 30 Hz) and were accompanied by a simultaneous rapid and large rise in
[Ca2+]i (34 of 34 cells). By contrast, direct depolarizing current (0.7 nA, 1
s) induced spikes having short duration, during which time the spike firing
pattern was observed not to be significantly affected. When Na+ channels were
blocked by QX-314 applied intracellularly through the recording microelectrode
in the presence of GABAA receptor antagonists, broad spikes were frequently
generated by activation of synaptic inputs (32 of 33 cells). These broad
spikes were blocked by Cd2+ (200 M) or in Ca2+ free medium (6 of 6 cells) but
were resistant to either TTX (1 M ; 6 of 6 cells) or QX-314, while short-
duration spikes were blocked by both TTX and QX-314. Based on these findings
we conclude that broad and short-duration spikes are Ca2+ and Na+ spikes,
respectively. To investigate the properties of the Ca2+ spikes, antagonists of
a voltage-operated Ca2+ channel were applied to the evoked responses.
Nifedipine (30 M), a L-type Ca2+ channel blocker, suppressed the generation of
Ca2+ spikes, whereas Ni2+ (100 M ), the T- and R-type Ca2+ channel blocker,
and -Agatoxin-IVA (-Aga-IVA, 60 nM), a P-type Ca2+ channel blocker, had little
effect on the generation of Ca2+ spikes. Nifedipine suppressed the rise in
[Ca2+]i induced by synaptic inputs up to 26 % of the control in the soma and
18-32 % in the dendrites (n = 5), respectively, whereas Ni2+ suppressed the
rise by 12-27 % (n = 5) in both soma and dendrites. -Aga-IVA showed little
effect (less than a 10% change; n = 7). These results suggest that the GABAA
inhibitory system tonically suppresses dendritic Ca2+ spikes, and the L-type
Ca2+ channel plays a major role in the generation of Ca2+ spikes and in Ca2+
influx.
Received 13 August 1996; accepted in final form 15 July 1997.
APS Manuscript Number J654-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997