Role of channels in the O permeability of murine red blood cells II. Morphological and proteomic studies.

In this second of three papers, we examine red blood cell (RBC) morphometry and RBC-membrane proteomics from our laboratory mouse strain (C57BL/6). In paper #1, using stopped-flow absorbance spectroscopy to ascertain the rate constant for oxyhemoglobin (HbO) deoxygenation , we find substantial reductions with (1) membrane-protein inhibitors p-chloromercuribenzenesulfonate (pCMBS) or 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS); (2) knockouts of aquaporin-1 (AQP1-KO), or Rhesus blood-group-associated A-glycoprotein (RhAG-KO), or double knockouts (dKO); or (3) inhibitor+dKO. In paper #3, reaction-diffusion mathematical modeling/simulations reveal that could fall secondary to slowed intracellular O/HbO/Hb diffusion.

Resting-State Functional Connectivity of Sensorimotor and Default Mode Networks and Lower Limb Performance in Chronic Stroke: A Cross-Sectional Study.

Introduction: Stroke disrupts functional brain connectivity, yet how this relates to lower limb motor and sensory abilities is not well understood. Greater knowledge of movement-related brain connectivity can aide in the development of better interventions for recovery after stroke. Our objective was to evaluate the relationship between lower limb performance and resting-state functional connectivity (rsFC) of large-scale brain networks for individuals with chronic motor deficits (> 6 months) after stroke.

Effects of extracellular metabolic acidosis and out-of-equilibrium CO/HCO solutions on intracellular pH in cultured rat hippocampal neurons.

Metabolic acidosis (MAc)-an extracellular pH (pH) decrease caused by a [HCO ] decrease at constant [CO]-usually causes intracellular pH (pH) to fall. Here we determine the extent to which the pH decrease depends on the pH decrease vs the concomitant [HCO ] decrease. We use rapid-mixing to generate out-of-equilibrium CO/HCO solutions in which we stabilize [CO] and [HCO ] while decreasing pH (pure acidosis, pAc), or stabilize [CO] and pH while decreasing [HCO ] (pure metabolic/down, pMet↓).

Role of Cl -HCO exchanger AE3 in intracellular pH homeostasis in cultured murine hippocampal neurons, and in crosstalk to adjacent astrocytes.

Key Points: A polymorphism of human AE3 is associated with idiopathic generalized epilepsy. Knockout of AE3 in mice lowers the threshold for triggering epileptic seizures. The explanations for these effects are elusive.

Soluble prion protein and its N-terminal fragment prevent impairment of synaptic plasticity by Aβ oligomers: Implications for novel therapeutic strategy in Alzheimer's disease.

The pathogenic process in Alzheimer's disease (AD) appears to be closely linked to the neurotoxic action of amyloid-β (Aβ) oligomers. Recent studies have shown that these oligomers bind with high affinity to the membrane-anchored cellular prion protein (PrP(C)). It has also been proposed that this binding might mediate some of the toxic effects of the oligomers.

Effects of metabolic acidosis on intracellular pH responses in multiple cell types.

Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3 (-)]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (ΔpHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes.

Intracellular pH regulation by acid-base transporters in mammalian neurons.

Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (J L) and extrusion (J E).