Permeant cations modulate pore dynamics and gating of TRPV1 ion channels.

The transient receptor vanilloid 1 (TRPV1) is a non-selective ion channel, which is activated by several chemical ligands and heat. We have previously shown that activation of TRPV1 by different ligands results in single-channel openings with different conductance, suggesting that the selectivity filter is highly dynamic. TRPV1 is weakly voltage dependent; here, we sought to explore whether the permeation of different monovalent ions could influence the voltage dependence of this ion channel. By using single-channel recordings, we show that TRPV1 channels undergo rapid transitions to closed states that are directly connected to the open state, which may result from structural fluctuations of their selectivity filter. Moreover, we demonstrate that the rates of these transitions are influenced by the permeant ion, suggesting that ion permeation regulates the voltage dependence of these channels. Our data could be the basis for more detailed MD simulations exploring the permeation mechanism and how the occupancy of different ions alters the three-dimensional structure of the pore of TRPV1 channels.

Specific Localization of an Auto-inhibition Mechanism at Presynaptic Terminals of Identified Serotonergic Neurons.

Auto-regulation mechanisms in serotonergic neurons regulate their electrical activity and secretion. Since these neurons release serotonin from different structural compartments - including presynaptic terminals, soma, axons and dendrites - through different mechanisms, autoregulation mechanisms are also likely to be different at each compartment. Here we show that a chloride-mediated auto-inhibitory mechanism is exclusively localized at presynaptic terminals, but not at extrasynaptic release sites, in serotonergic Retzius neurons of the leech. An auto-inhibition response was observed immediately after intracellular stimulation with an electrode placed in the soma, in neurons that were isolated and cultured retaining an axonal stump, where presynaptic terminals are formed near the soma, but not in somata isolated without axon, where no synaptic terminals are formed, nor in neurons in the nerve ganglion, where terminals are electrotonically distant from the soma. Furthermore, no auto-inhibition response was detected in either condition during the longer time course of somatic secretion. This shows that the auto-inhibition effects are unique to nerve terminals. We further determined that serotonin released from peri-synaptic dense-core vesicles contributes to auto-inhibition in the terminals, since blockade of L-type calcium channels, which are required to stimulate extrasynaptic but not synaptic release, decreased the amplitude of the auto-inhibition response. Our results show that the auto-regulation mechanism at presynaptic terminals is unique and different from that described in the soma of these neurons, further highlighting the differences in the mechanisms regulating serotonin release from different neuronal compartments, which expand the possibilities of a single neuron to perform multiple functions in the nervous system.

What is new about mild temperature sensing? A review of recent findings.

The superfamily of Transient Receptor Potential (TRP) channels is composed by a group of calcium-permeable ionic channels with a generally shared topology. The thermoTRP channels are a subgroup of 11 members, found in the TRPA, TRPV, TRPC, and TRPM subfamilies. Historically, members of this subgroup have been classified as cold, warm or hot-specific temperature sensors. Recently, new experimental results have shown that the role that has been given to the thermoTRPs in thermosensation is not necessarily strict. In addition, it has been shown that these channels activate over temperature ranges, which can have variations depending on the species and the interaction with a specific biological context. Investigation of these interactions could help to elucidate the mechanisms of activation by temperature, which remains uncertain. Abbreviations: Cryo-EM: Cryogenic electron microscopy; DRG: Dorsal root ganglia; H: Human; ROS: Reactive Oxygen Species; TG: Trigeminal ganglia; TRP: Transient Receptor Potential; TRPA: TRP ankyrin; TRPV: TRP vanilloid; TRPC: TRP canonical; TRPM: TRP melastatin.