ABSTRACT
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 +/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma.
Subject(s)
Adenosine Triphosphate/metabolism , Autocrine Communication , Calcium/metabolism , Chloride Channels/metabolism , Hippocampus/cytology , Microglia/metabolism , Animals , Cell Line , Ion Channel Gating , Mice , Models, Biological , Purines/metabolismABSTRACT
OBJECTIVES: The study evaluated the role of the autonomic nervous system in atrial fibrillation (AF) recurrence. BACKGROUND: Early recurrence of AF after cardioversion (CV) is attributed to electrical remodeling. The possibility that an abnormal autonomic modulation might contribute to this phenomenon has not yet been adequately tested. METHODS: We analyzed short-term heart rate variability (HRV) in 93 patients with persistent AF and on chronic amiodarone treatment, after restoration of sinus rhythm by electrical CV. RESULTS: Two weeks later, 25 patients presented with AF. Spectral analysis of HRV revealed that patients wi
