The Journal of Neurophysiology Vol. 78 No. 5 November 1997, pp. 2269-2279
Copyright ©1997 The American Physiological Society

Properties of Calcium Spikes Revealed During GABA_A Receptor Antagonism in Hippocampal CA1 Neurons From Guinea Pigs

Masami Miura¹, Masatomo Yoshioka¹, Hiroyoshi Miyakawa², Hiroshi Kato¹, and Ken-Ichi Ito¹

¹ Department of Physiology, Yamagata University School of Medicine, Yamagata 990-23; and ² Laboratory of Life Science, School of Life Science, Tokyo College of Pharmacy, Hachioji 192-03, Japan

Miura, Masami, Masatomo Yoshioka, Hiroyoshi Miyakawa, Hiroshi Kato, and Ken-Ichi Ito. Properties of calcium spikes revealed during GABA_A receptor antagonism in hippocampal CA1 neurons from guinea pigs. J. Neurophysiol. 78: 2269-2279, 1997. Intracellular electrical responses and changes in intracellular calcium concentration ([Ca²⁺]_i) in response to activation of synaptic inputs and to DC injections were recorded simultaneously from CA1 pyramidal neurons (n = 42) in guinea pig hippocampal slices. In the presence of the -aminobutyric acid-A (GABA_A) receptor antagonists, bicuculline (25 µM) and picrotoxin (10 µM), 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 GABA_A receptor antagonists, broad spikes were frequently generated by activation of synaptic inputs (32 of 33 cells). These broad spikes were blocked by Cd²⁺ (200 µM) or in Ca²⁺-free medium (6 of 6 cells) but were resistant to either tetrodotoxin (TTX; 1 µM; 6 of 6 cells) or QX-314, whereas short-duration spikes were blocked by both TTX andQX-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 µM), a L-type Ca²⁺ channel blocker, suppressed the generation of Ca²⁺ spikes, whereas Ni²⁺ (100 µM), theT- 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 GABA_A 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.

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