Ca¥ plays a major role in stimulus-response coupling. In electrically non-excitable cells, the activation of receptors linked to phospholipid hydrolysis evokes a biphasic increase in the concentration of cytoplasmic free Ca¥ ([Ca¥]é). The first phase is due to the stimulation by inositol 1,4,5_tris-phosphate (IP3) of Ca¥ release from intracellular Ca¥ stores. The second phase results from an entry of Ca¥ across the plasma membrane (Berridge, 1993 [Ca¥]i, but had little (at 10 mÒ K¤) or no effect on the plateau level. This confirms that the capacitative Ca¥ entry is small. 4. In clusters of cells whose membrane potential was not clamped with diazoxide, 15 mÒ glucose (in 4·8 mÒ K¤) induced [Ca¥]é oscillations by promoting Ca¥ influx through voltagedependent Ca¥ channels. The application of thapsigargin accelerated these oscillations and increased their amplitude, sometimes causing a sustained elevation of [Ca¥]i. Similar results were obtained from whole islets perifused with a medium containing ü 6 mÒ glucose. The effect of thapsigargin was always much larger than expected from the capacitative Ca¥ entry, probably because of a potentiation of Ca¥ influx through voltage-dependent Ca¥ channels. 5. This potentiating effect of thapsigargin did not result from an acceleration of cell metabolism since the drug did not affect glucose-induced changes in NAD(P)H fluorescence. It is also unlikely to involve the inhibition of KATP channels because thapsigargin steadily elevated [Ca¥]é in cells in which [Ca¥]é oscillations persisted in the presence of a maximally effective concentration of tolbutamide. 6. In conclusion, the emptying of intracellular Ca¥ stores in â-cells induces a small capacitative Ca¥ entry and activates a depolarizing current which potentiates glucose-induced Ca¥ influx through voltage-dependent Ca¥ channels.

No abstract

The medial prefrontal cortex (mPFC) has been proposed to be essential for extinction of fear memory, but its neural mechanism has been poorly understood. The present study examined whether synaptic transmission in the hippocampal-mPFC pathway is related to extinction of context-dependent fear memory in freely moving rats using electrophysiological approaches combined with behavioral analysis. Population spike amplitude in the mPFC was decreased during the first extinction trial by exposure to contextual fear conditioning. This synaptic inhibition was reversed by repeated extinction trials, accompanied by decreases in fear-related freezing behavior. These results suggest that alteration of synaptic transmission in the hippocampal-mPFC pathway is associated with the extinction processes of context-dependent fear memory. Further experiments were performed to elucidate whether early postnatal stress alters the synaptic response in the mPFC during extinction trials using a juvenile stress model, based on our previous findings that early postnatal stress affects the behavioral response to emotional stress. Adult rats that previously were exposed to five footshocks (FS) (shock intensity, 0.5 mA; intershock interval, 28 seconds; shock duration, 2 seconds) at postnatal day 21 to 25 (week 3; 3W-FS) exhibited impaired reversal of both inhibitory synaptic transmission and freezing behavior induced by repeated extinction trials. The neuronal and behavioral deficits observed in the 3W-FS group were prevented by pretreatment with the serotonin(1A) receptor agonist tandospirone (1 mg/kg, i.p.). These results indicate the possiblity that aversive stress exposure during the third postnatal week impaired extinction processes of context-dependent fear memory. The deficits in extinction observed in the 3W-FS group might be attributable to dysfunction of hippocampal-mPFC neural circuits involving 5-HT(1A) receptor mechanisms.

Outcome from near-complete but not incomplete cerebral ischemia depended on the anesthetic agent administered during the ischemic insult.

Only Glycer-AGE has a proliferative effect on HuH7, which expresses a higher level of RAGE. MK615 suppresses the proliferative effect of Glycer-AGE on HuH7 by decreasing the expression of RAGE.