Somatostatin Modulates High Voltage-Activated Ca2+ Channels in Freshly Dissociated Rat Hippocampal Neurons. ISHIBASHI, HITOSHI AND NORIO AKAIKE. Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka 812-82, Japan.
APStracts 2:0139N, 1995.
SUMMARY AND CONCLUSIONS
1. The effects of somatostatin (SS) on the low- and high-voltage activated Ca2+ channels in the pyramidal neurons acutely dissociated from the hippocampal CA1 region of two- to three-week old rats were investigated in a nystatin perforated patch recording configuration under voltage-clamp conditions. 2. SS had no effect on the low voltage-activated (LVA) Ca2+ channel but did inhibit the high voltage-activated (HVA) Ca2+ channel in a concentration-, time- and voltage-dependent manner. 3. SS slowed the activation phase of Ba2+ current passing through HVA Ca2+ channels and the maximum inhibition was 28 % of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. Pretreatment with pertussis toxin (PTX) completely blocked the SS effect on HVA Ba2+ current (IBa), suggesting the contribution of PTX-sensitive Gi/Go-proteins to the SS-induced inhibition. 4. The applications of forskolin, 8-Br-cAMP, dibutyryl-cGMP, staurosporine and H- 7 did not affect either the control HVA IBaor the SS-induced inhibition of HVA IBa. 5. Pretreatment with protein kinase C (PKC) activators had no significant effect on HVA IBa but did remove the inhibition of HVA IBa by SS. 6. w- Conotoxin-GVIA, w-agatoxin-IVA, nicardipine and w-conotoxin-MVIIC blocked HVA IBa by 27, 13, 38 and 9 % of the total HVA current respectively, which suggested the existence of N-, P-, L- and Q-type HVA Ca2+ channels in the hippocampal CA1 pyramidal neurons. A current that was insensitive to these Ca2+ channel antagonists, termed an R-type HVA Ca2+ channel current, was also found to exist. This residual R-type Ca2+ channel was completely blocked by adding 200 mM Cd2+. 7. The SS significantly inhibited only the N-type HVA Ca2+ channel, which is one of the five types of HVA Ca2+ channels. 8. The above results suggest that SS selectively inhibits the N-type HVA Ca2+ channel via the PTX sensitive Gi/Go-protein in the hippocampal CA1 pyramidal neurons while the SS-induced inhibition is also regulated by the PKC-mediated pathway. 

Received 12 December 1994; accepted in final form 25 April 1995.
APS Manuscript Number J773-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.