AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 20:40:35
Voltage Sensing in Thermo-TRP Channels
Sebastian Brauchi and Patricio Orio
Membrane voltage, ligand binding, mechanical force and temperature can all induce conformational changes that open ion channel pores. A key question in understanding ion channel function is how the protein domains involved in sensing stimuli (sensors) communicate with the pore to gate its opening and closing. TRP channels are considered six-transmembrane cation-permeable channels, distant relatives of voltage-gated potassium channels (Kv), which are known to be activated by membrane depolarization. Understanding the molecular nature of thermo-TRP channel gating offers a fair challenge to biophysicists. This chapter will summarize our present knowledge on the effect of voltage and temperature during thermo-TRP channel activation.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 20:35:29
TRP Channels as Mediators of Oxidative Stress
Barbara A. Miller and Wenyi Zhang
The transient receptor potential (TRP) protein superfamily is a diverse group of cation-permeable channels expressed in mammalian cells, which is divided into six subfamilies based on sequence identity. Three subfamilies have members with roles in oxidative stress: the TRPC subfamily characterized by receptor operated calcium entry channels; the TRPM subfamily with a number of members involved in cell proliferation and death; and the TRPV subfamily which is activated by chemical, mechanical, and physical stimuli. The TRPC members TRPC3 and TRPC4 can serve as subunits of a redox-sensitive ion channel in native aortic endothelial cells. The TRPM family member TRPM2 has a number of physiologic isoforms expressed in many cell types and responds to stimuli including oxidative stress, TNFα, and β-amyloid peptide. The important role of TRPM2 isoforms in cell proliferation and oxidant-induced cell death has been well established using divergent cell systems and techniques including overexpression, channel depletion or inhibition, and calcium chelation. TRPM7 has been shown to be involved in Ca2+ influx and anoxic cell death in cortical neurons. In these cells and in B cells, precise expression of TRPM7 is necessary for cell survival. TRPV1 is involved in oxidant stress-induced pain and in neuronal injury, contributing to diabetic sensory neuropathy. Future studies will likely identify additional channels involved in oxidant injury, as well as better define mechanisms through which these channels are regulated and mediate their effects. Therapeutic approaches to modulate activation of specific TRP channels are likely to have an important impact in reducing tissue damage in a number of diseases resulting from oxidant stress including ischemia/reperfusion injury and diabetes.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 20:28:33
Regulation of TRP Signalling by Ion Channel Translocation Between Cell Compartments
Alexander C. Cerny and Armin Huber
The TRP (transient receptor potential) family of ion channels is a heterogeneous family of calcium permeable cation channels that is subdivided into seven subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM
("Melastatin"), TRPA ("Ankyrin"), TRPN ("NOMPC"), TRPP ("Polycystin"), and TRPML ("Mucolipin"). TRP-mediated ion currents across the cell membrane are determined by the single channel conductance, by the fraction of activated channels, and by the total amount of TRP channels present at the plasma membrane. In many cases, the amount of TRP channels at the plasma membrane is altered in response to physiological stimuli by translocation of channels to and from the plasma membrane. Regulated translocation has been described for channels of the TRPC, TRPV, TRPM, and TRPA family and is achieved by vesicular transport of these channels along cellular exocytosis and endocytosis pathways. This review summarizes the stimuli and signalling cascades involved in the translocation of TRP channels and highlights interactions of TRP channels with proteins of the endocytosis and exocytosis machineries.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 20:23:48
Emerging Roles of Canonical TRP Channels in Neuronal Function
Sunitha Bollimuntha, Senthil Selvaraj, and Brij B. Singh
Ca2+ signaling in neurons is intimately associated with the regulation of vital physiological processes including growth, survival and differentiation. In neurons, Ca2+ elicits two major functions. First as a charge carrier, Ca2+ reveals an indispensable role in information relay via membrane depolarization, exocytosis, and the release of neurotransmitters. Second on a global basis, Ca2+ acts as a ubiquitous intracellular messenger to modulate neuronal function. Thus, to mediate Ca2+-dependent physiological events, neurons engage multiple mode of Ca2+ entry through a variety of Ca2+ permeable plasma membrane channels. Here we discuss a subset of specialized Ca2+-permeable non-selective TRPC channels and summarize their physiological and pathological role in the context of excitable cells. TRPC channels are predominately expressed in neuronal cells and are activated through complex mechanisms, including second messengers and store depletion. A growing body of evidence suggests a prime contribution of TRPC channels in regulating fundamental neuronal functions. TRPC channels have been shown to be associated with neuronal development, proliferation and differentiation. In addition, TRPC channels have also been suggested to have a potential role in regulating neurosecretion, long term potentiation, and synaptic plasticity. During the past years, numerous seminal discoveries relating TRPC channels to neurons have constantly emphasized on the significant contribution of this group of ion channels in regulating neuronal function. Here we review the major groundbreaking work that has uniquely placed TRPC channels in a pivotal position for governing neuronal Ca2+ signaling and associated physiological responses.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 19:37:50
TRP Channels and Neural Persistent Activity
Antonio Reboreda, Lydia Jiménez-Díaz, and Juan D. Navarro-López
One of the integrative properties of the nervous system is its capability to, by transient motor commands or brief sensory stimuli, evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. This neural activity, named persistent activity, is found in a good number of brain regions and is thought to be a neural substrate for short-term storage and accumulation of sensory or motor information . Examples of this persistent neural activity have been reported in prefrontal  and entorhinal  cortices, as part of the neural mechanisms involved in short-term working memory . Interestingly, the general organization of the motor systems assumes the presence of bursts of short-lasting motor commands encoding movement characteristics such as velocity, duration, and amplitude, followed by a maintained tonic firing encoding the position at which the moving appendage should be maintained [5, 6]. Generation of qualitatively similar sustained discharges have also been found in spinal and supraspinal regions in relation to pain processing [7, 8]. Thus, persistent neural activity seems to be necessary for both behavioral (positions of fixation) and cognitive (working memory) processes. Persistent firing mechanisms have been proposed to involve the participation of a non-specific cationic current (CAN current) mainly mediated by activation of TRPC channels. Because the function and generation of persistent activity is still poorly understood, here we aimed to review and discuss the putative role of TRP-like channels on its generation and/or maintenance.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 19:01:39
Role of TRP Channels in Pain Sensation
Man-Kyo Chung, Sung Jun Jung, and Seog Bae Oh
It is crucial for a living organism to recognize and discern potentially harmful noxious stimuli from innocuous stimuli to avoid hazards in the environment. However, unnecessary or exaggerated nociception is at best unpleasant and often compromises the quality of life. In order to lessen the intensity of nociception or eliminate the pathological pain, it is important to understand the nature of nociception and the mechanisms of hyperalgesia or allodynia. Transient receptor potential (TRP) channels play central roles in nociception under physiological and pathological conditions including inflammation and neuropathy. In this chapter, we will highlight the enormous progress in understanding the role of TRP channels in nociception. We will mainly focus on two TRP channels (TRPV1 and TRPA1) that have been particularly implicated in transducing signals associated with pain sensation, and briefly discuss the role of TRPM8, TRPV3 and TRPV4. We will stress debatable issues that needed to be resolved and provide perspectives for the future studies.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 18:56:41
TRPV1: A Therapy Target That Attracts the Pharmaceutical Interests
Rong Xia, Kim Dekermendjian, Elke Lullau, and Niek Dekker
TRPV1 is a non-selective cation channel gated by noxious heat, vanilloids and extracellular protons, and act as an important signal integrator in sensory nociceptors. Because of its integrative signaling properties in response to inflammatory stimuli, TRPV1 antagonists are predicted to inhibit the sensation of ongoing or burning pain that is reported by patients suffering from chronic pain, therefore offering an unprecedented advantage in selectively inhibiting painful signaling from where it is initiated. In this chapter, we firstly summarize the physiological and pathological roles of TRPV1 and then describe the pharmacology of TRPV1 agonists and antagonists. Finally, we give an update and the status on TRPV1 therapies that have progressed into clinical trials.
AbstractsPosted by Md. Shahidul Islam Sun, February 06, 2011 18:34:01
Expression and Function of TRP Channels in Liver Cells
Grigori Y. Rychkov and Gregory J. Barritt
The liver plays a central role in whole body homeostasis by mediating the metabolism of carbohydrates, fats, proteins, drugs and xenobiotic compounds, and bile acid and protein secretion. Hepatocytes together with endothelial cells, Kupffer cells, smooth muscle cells, stellate and oval cells comprise the functioning liver. Many members of the TRP family of proteins are expressed in hepatocytes. However, knowledge of their cellular functions is limited. There is some evidence which suggests the involvement of TRPC1 in volume control, TRPV1 and V4 in cell migration, TRPC6 and TRPM7 in cell proliferation, and TRPPM in lysosomal Ca2+ release. Altered expression of some TRP proteins, including TRPC6, TRPM2 and TRPV1, in tumorigenic cell lines may play roles in the development and progression of hepatocellular carcinoma and metastatic liver cancers. It is likely that future experiments will define important roles for other TRP proteins in the cellular functions of hepatocytes and other cell types of which the liver is composed.