Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord

Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. In periphery, they contribute to sensory transmission, including that of nociception and pain. Here we characterized ASIC-like currents in dorsal horn neurons of the rat spinal cord and their functional modulation in pathological conditions. Reverse transcriptase-nested PCR and Western blotting showed that three ASIC isoforms, ASIC1a, ASIC2a, and ASIC2b, are expressed at a high level in dorsal horn neurons. Electrophysiological and pharmacological properties of the proton-gated currents suggest that homomeric ASIC1a and/or heteromeric ASIC1a + 2b channels are responsible for the proton-induced currents in the majority of dorsal horn neurons. Acidification-induced action potentials in these neurons were compatible in a pH-dependent manner with the pH dependence of ASIC-like current. Furthermore, peripheral complete Freund's adjuvant-induced inflammation resulted in increased expression of both ASIC1a and ASIC2a in dorsal horn. These results support the idea that the ASICs of dorsal horn neurons participate in central sensory transmission/modulation under physiological conditions and may play important roles in inflammation-related persistent pain.

Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death

Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASICla-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca2+ elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis.

Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity

Development of chronic pain involves alterations in peripheral nociceptors as well as elevated neuronal activity in multiple regions of the CNS. Previous pharmacological and behavioral studies suggest that peripheral acid-sensing ion channels (ASICs) cont

Fabrication of high-Q film bulk acoustic resonator (FBAR) filters withcarbon nanotube (CNT) electrodes

FBAR devices with carbon nanotube (CNT) electrodes have been developed withthe aim of taking advantage of the low density and high acoustic impedance ofthe CNTs compared to other known materials. The influence of the CNTs on thefrequency response of the FBAR devices was studied by comparing two identicalsets of devices, one set comprised FBARs fabricated with chromium/gold bilayerelectrodes, and the second set comprised FBARs fabricated with CNT electrodes.It was found that the CNTs had a significant effect on attenuating travellingwaves at the surface of the FBARs membranes due to their high elastic stiffness.Finite element analysis of the devices fabricated was carried out using COMSOLMultiphysics, and the numerical results confirmed the experimental resultsobtained. © 2010 IEEE.

Eccentricity effects on acoustic radiation from a spherical source suspended within a thermoviscous fluid sphere.

Acoustic radiation from a spherical source undergoing angularly periodic axisymmetric harmonic surface vibrations while eccentrically suspended within a thermoviscous fluid sphere, which is immersed in a viscous thermally conducting unbounded fluid medium, is analyzed in an exact fashion. The formulation uses the appropriate wave-harmonic field expansions along with the translational addition theorem for spherical wave functions and the relevant boundary conditions to develop a closed-form solution in form of infinite series. The analytical results are illustrated with a numerical example in which the vibrating source is eccentrically positioned within a chemical fluid sphere submerged in water. The modal acoustic radiation impedance load on the source and the radiated far-field pressure are evaluated and discussed for representative values of the parameters characterizing the system. The proposed model can lead to a better understanding of dynamic response of an underwater acoustic lens. It is equally applicable in miniature transducer analysis and design with applications in medical ultrasonics.