Itzchak Parnas

Nathan Dascal3
Yair Ben-Chaim3
Francisco Bezanilla2
3Nathan Dascal
3Yair Ben-Chaim
2Francisco Bezanilla
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Activation by agonist binding of G-protein-coupled receptors (GPCRs) controls most signal transduction processes. Although these receptors span the cell membrane, they are not considered to be voltage sensitive. Recently it was shown that both the activity of GPCRs and their affinity towards agonists are regulated by membrane potential. However, it remains(More)
G-protein coupled receptors are not considered to exhibit voltage sensitivity. Here, using Xenopus oocytes, we show that the M2 muscarinic receptor (m2R) is voltage-sensitive. The m2R-mediated potassium channel (GIRK) currents were used to assay the activity of m2R. We found that the apparent affinity of m2R toward acetylcholine (ACh) was reduced upon(More)
G-protein-coupled receptors play a key role in signal transduction processes. Despite G-protein-coupled receptors being transmembrane proteins, the notion that they exhibit voltage sensitivity is rather novel. Here we examine whether two metabotropic glutamate receptors, mGluR3 and mGluR1a, both involved in fundamental physiological processes, exhibit, by(More)
G protein-coupled receptors play a central role in signal transduction and were only known to be activated by agonists. Recently it has been shown that membrane potential also affects the activity of G protein-coupled receptors. For the M(2) muscarinic receptor, it was further shown that depolarization induces charge movement. A tight correlation was found(More)
Reliable neuronal communication depends on accurate temporal correlation between the action potential and neurotransmitter release. Although a requirement for Ca(2+) in neurotransmitter release is amply documented, recent studies have shown that voltage-sensitive G protein-coupled receptors (GPCRs) are also involved in this process. However, how slow-acting(More)
This review discusses two theories that try to explain mechanisms of control of neurotransmitter release in fast synapses: the Ca(2+) hypothesis and the Ca(2+) voltage hypothesis. The review summarizes experimental results that are incompatible with predictions from the Ca(2+) hypothesis and concludes that Ca(2+) is involved in the control of the amount of(More)
Ca(2+) is essential for physiological depolarization-evoked synchronous neurotransmitter release. But, whether Ca(2+) influx or another factor controls release initiation is still under debate. The time course of ACh release is controlled by a presynaptic inhibitory G protein-coupled autoreceptor (GPCR), whose agonist-binding affinity is voltage-sensitive.(More)
This review describes the development of the molecular level Ca(2+)-voltage hypothesis. Theoretical considerations and feedback between theory and experiments played a key role in its development. The theory, backed by experiments, states that at fast synapses, membrane potential by means of presynaptic inhibitory autoreceptors controls initiation and(More)
The effect of membrane potential on feedback inhibition of acetylcholine (ACh) release was studied using the frog neuromuscular junction. It was found that membrane potential affects the functional affinity (K(i)) of the presynaptic M2 muscarinic receptor. The K(i) for muscarine shifts from approximately 0.23 microm (at resting potential) to approximately 8(More)
G-protein coupled receptors (GPCRs) comprise the largest protein family and mediate the vast majority of signal transduction processes in the body. Until recently GPCRs were not considered to be voltage dependent. Newly it was shown for several GPCRs that the first step in GPCR activation, the binding of agonist to the receptor, is voltage sensitive:(More)