PubMed · 4307020
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D R Curtis, J M Crawford. 1969. Central synaptic transmission--microelectrophoretic studies.. https://doi.org/10.1146/annurev.pa.09.040169.001233
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
1. Intercellular electrical communication between smooth muscle and endothelial cells was examined in guinea-pig mesenteric arterioles using the whole-cell patch-clamp method. The time course of the current required to impose a 10 mV voltage clamp step was used to determine the extent of electrical coupling between them. Currents recorded from both smooth muscle and endothelial cells relaxed in a multi-exponential manner, indicating the existence of electrical coupling between cells. 2. 18beta-Glycyrrhetinic acid, a gap junction blocker, quickly blocked electrical communication at 40 microM, while neither heptanol nor octanol did so at concentrations of up to 1 mM. 3. In the current clamp mode, repetitive spikes, induced by 10 mM Ba2+ solutions, could be recorded from both kinds of cells. After blocking gap junctions, spikes could only be recorded from the smooth muscle cell layer, indicating that they had been conducted through myoendothelial junctions. 4. In endothelial cells, acetylcholine (ACh, 3 microM) induced hyperpolarizing responses, which had two phases (an initial fast and a second slower phase) in the current clamp condition. This ACh response persisted in the presence of 18beta-glycyrrhetinic acid, although this compound seemed to make the membrane slightly leaky. 5. After blocking gap junctions, the membrane potential of a single cell in a multicellular preparation could be well clamped. Thus, 18beta-glycyrrhetinic acid may be useful in studying the function of both arteriolar smooth muscle and endothelial cells while they remain located within a multicellular preparation.
Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, brain-derived neurotrophic factor augmented glutamate-evoked, but not acetylcholine-evoked, currents 3-fold and increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate currents were not affected by nerve growth factor or NT-3, and increased open probability was prevented by the tyrosine kinase inhibitor K-252a. In addition, the NMDA receptor antagonist MK-801 blocked brain-derived neurotrophic factor enhancement of synaptic transmission, further suggesting that NTs modulate synaptic efficacy via changes in NMDA receptor function.
Zn2+ is a key structural/functional component of many proteins and is present at high concentrations in the brain and retina, where it modulates ligand-gated receptors. Therefore, a study was made of the effects of zinc on homomeric neuronal nicotinic receptors expressed in Xenopus oocytes after injection of cDNAs encoding the chicken wild or mutant alpha7 subunits. In oocytes expressing wild-type receptors, Zn2+ alone did not elicit appreciable membrane currents. Acetylcholine (AcCho) elicited large currents (IAcCho) that were reduced by Zn2+ in a reversible and dose-dependent manner, with an IC50 of 27 microM and a Hill coefficient of 0.4. The inhibition of IAcCho by Zn2+ was competitive and voltage-independent, a behavior incompatible with a channel blockade mechanism. In sharp contrast, in oocytes expressing a receptor mutant, with a threonine-for-leucine 247 substitution (L247Talpha7), subnanomolar concentrations of Zn2+ elicited membrane currents (IZn) that were reversibly inhibited by the nicotinic receptor blockers methyllycaconitine and alpha-bungarotoxin. Cell-attached single-channel recordings showed that Zn2+ opened channels that had a mean open time of 5 ms and a conductance of 48 pS. At millimolar concentrations Zn2+ reduced IAcCho and the block became stronger with cell hyperpolarization. Thus, Zn2+ is a reversible blocker of wild-type alpha7 receptors, but becomes an agonist, as well as an antagonist, following mutation of the highly conserved leucine residue 247 located in the M2 channel domain. We conclude that Zn2+ is a modulator as well as an activator of homomeric nicotinic alpha7 receptors.