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L G Wu

Publications and source records attributed to L G Wu.

22 records · Page 2Linked to original sources

Pharmacological identification of two types of presynaptic voltage-dependent calcium channels at CA3-CA1 synapses of the hippocampus.

The effects of voltage-dependent Ca channel (VDCC) antagonists on synaptic transmission were investigated at CA3-CA1 synapses of guinea pig hippocampal slices. After selectively loading presynaptic structures in area CA1 with the calcium indicator fura-2, we simultaneously recorded a presynaptic calcium transient ([Ca]t) and the corresponding field excitatory postsynaptic potential (fEPSP) evoked by a single stimulus given to the Schaffer collateral-commissural (SCC) pathway. Application of nifedipine did not reduce either the [Ca]t of the fEPSP, suggesting that nifedipine-sensitive Ca channels do not significantly contribute to evoked synaptic transmission at low stimulation frequency. Application of omega-conotoxin GVIA (omega-CgTX) or omega-agatoxin-IVA (omega-Aga-IVA) dose-dependently blocked both the [Ca]t and the fEPSP. The time course of the block of the [Ca]t was similar to that of the fEPSP. About 40% of the total [Ca]t was omega-CgTX sensitive, and more than 20% was omega-Aga-IVA sensitive. Combined application of these two blockers showed no overlap of the omega-CgTX-sensitive with the omega-Aga-IVA-sensitive [Ca]t. These results suggest that there are at least two types of presynaptic VDCCs at CA3-CA1 synapses of the hippocampus: omega-CgTX-sensitive and omega-Aga-IVA-sensitive Ca channels. Our results also suggest that these two types of Ca channels are colocalized at a single presynaptic terminal. During application of omega-CgTX or omega-Aga-IVA, the initial slope of the fEPSP varied approximately as the fourth power of the amplitude of the [Ca]t, suggesting that omega-CgTX-sensitive and omega-Aga-IVA-sensitive Ca channels have about equal efficacy in triggering transmitter release. These results in combination with similar findings at the squid giant synapse suggest that the nonlinear relationship between transmitter release and the Ca influx is well conserved from the molluscan to the mammalian nervous system.

Animals↗

An electrophysiological study on the membrane receptor-mediated action of glucocorticoids in mammalian neurons.

The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell's input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca2+/high Mg2+ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10(-7) M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Rapid membrane effects of adrenocorticoids on celiac ganglion cells of guinea pig].

Intracellular recording technique was used to determine the effects of corticosterone, dexamethasone, aldosterone and cholesterol on the resting membrane potentials and membrane resistance of cells in isolated celiac ganglion of guinea pigs. Hyperpolarization was elicited by corticosterone in 15 out of 83 cells, but was not caused by dexamethasone, which depolarized the membrane in 2 out of 18 cells. In addition, depolarization was also elicited by corticosterone in 2 out of 83 cells. Aldosterone and cholesterol caused no detectable changes of membrane potential and membrane resistance. It is suggested that the membrane effects of adrenocorticoids, which obviously could not be explained by traditional genomic mechanism for their short latency, may indicate the existence of membrane receptors for adrenocorticoids in celiac ganglion neurons of guinea pigs.

Aldosterone↗