GABAR silencing of nerve terminals.

Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Presynaptic G-protein coupled receptors (GPCRs) are critical in this problem as they locally influence synaptic strength and can operate on a wide range of time scales. Among the mechanisms by which GPCRs impact neurotransmission is by inhibiting voltage-gated calcium (Ca) influx in the active zone.

Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels.

Pain is a prevalent biopsychosocial condition that poses a significant challenge to healthcare providers, contributes substantially to a disability, and is a major economic burden worldwide. An overreliance on opioid analgesics, which primarily target the μ-opioid receptor, has caused devastating morbidity and mortality in the form of misuse and overdose-related death. Thus, novel analgesic medications are needed that can effectively treat pain and provide an alternative to opioids.

Role of specific presynaptic calcium channel subtypes in isoflurane inhibition of synaptic vesicle exocytosis in rat hippocampal neurones.

Background: P/Q- and N-type voltage-gated calcium channels (VGCC) are the principal subtypes mediating synaptic vesicle (SV) exocytosis. Both the degree of isoflurane inhibition of SV exocytosis and VGCC subtype expression vary between brain regions and neurotransmitter phenotype. We hypothesised that differences in VGCC subtype expression contribute to synapse-selective presynaptic effects of isoflurane.

Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling.

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.

Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment.

The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors.