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Modulatory mechanisms of nociceptive TRP channels
Maršáková, Lenka ; Vlachová, Viktorie (advisor) ; Novotný, Jiří (referee) ; Zemková, Hana (referee)
Detection of painful stimuli in the periphery is mediated by temperature-sensitive transient receptor potential (TRP) channels which are expressed in primary afferent endings of free sensory neurons called nociceptors. TRP channels in nociceptors are involved in the detection of thermal, but also mechanical and chemical stimuli. Out of seven known types of temperature-sensitive TRP channels, three are responsible for detecting painful temperatures: vanilloid receptors TRPV1 (> 42 o C) and TRPV2 (> 52 o C) detect noxious heat, and ankyrin receptor TRPA1 detects noxious cold (< 17 o C). Better knowledge of TRP channel mechanisms of action is essential for understanding TRP channel functions and ultimately for the design of potential analgesics. New findings presented in this thesis clarify mechanisms of action of TRPV1 and TRPA1 receptors, focusing on camphor and voltage sensitivity of TRPV1 channels and calcium modulation of TRPA1 channels. The first topic discussed in this thesis is the mechanism of camphor sensitivity of TRPV1 receptor. Camphor is a naturally occurring substance known since time immemorial for its effective analgesic properties, yet its mechanism of action is not understood. Camphor is known to be a partial agonist of TRPV1 channel, a full agonist of TRPV3 channel, but also an inhibitor of...
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Modulatory mechanisms of nociceptive TRP channels
Maršáková, Lenka
Detection of painful stimuli in the periphery is mediated by temperature-sensitive transient receptor potential (TRP) channels which are expressed in primary afferent endings of free sensory neurons called nociceptors. TRP channels in nociceptors are involved in the detection of thermal, but also mechanical and chemical stimuli. Out of seven known types of temperature-sensitive TRP channels, three are responsible for detecting painful temperatures: vanilloid receptors TRPV1 (> 42 o C) and TRPV2 (> 52 o C) detect noxious heat, and ankyrin receptor TRPA1 detects noxious cold (< 17 o C). Better knowledge of TRP channel mechanisms of action is essential for understanding TRP channel functions and ultimately for the design of potential analgesics. New findings presented in this thesis clarify mechanisms of action of TRPV1 and TRPA1 receptors, focusing on camphor and voltage sensitivity of TRPV1 channels and calcium modulation of TRPA1 channels. The first topic discussed in this thesis is the mechanism of camphor sensitivity of TRPV1 receptor. Camphor is a naturally occurring substance known since time immemorial for its effective analgesic properties, yet its mechanism of action is not understood. Camphor is known to be a partial agonist of TRPV1 channel, a full agonist of TRPV3 channel, but also an inhibitor of...
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Mechanisms of Activation and Modulation of Ion Channels Specific for Nociceptive Neurones
Touška, Filip ; Vlachová, Viktorie (advisor) ; Paleček, Jiří (referee) ; Tureček, Rostislav (referee)
Human body detects potentially damaging stimuli by specialized sensory nerve endings in the skin, the nociceptors. Their membranes are equipped with ion channels, molecular sensors, coding the outside stimuli into the trains of action potentials and conducting them to the higher brain centers. The most prominent group of transduction ion channels is the transient receptor potential (TRP) channel family followed by ion channels responsible for generation and conduction of action potentials from the periphery to the brain, the voltage-gated sodium channels (VGSCs). Understanding the mechanisms how particular stimulus is encoded and processed is of particular importance to find therapeutics for various types of pain conditions. We characterized the properties of VGSC subtypes NaV1.9 and NaV1.8 at high temperatures. We showed that NaV1.9 undergo large increase in current with increasing temperatures and significantly contribute to the action potential generation in dorsal root ganglion (DRG) neurons. Ciguatoxins (CTXs) are sodium channels activator toxins causing ciguatera fish poisoning, a disease manifested by sensory and neurological disturbances. We elucidated the mechanism of CTX- induced cold allodynia, a pathological phenomenon where normally innocuous cool temperatures are perceived as pain. We...
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Modulatory mechanisms of nociceptive TRP channels
Maršáková, Lenka ; Vlachová, Viktorie (advisor) ; Novotný, Jiří (referee) ; Zemková, Hana (referee)
Detection of painful stimuli in the periphery is mediated by temperature-sensitive transient receptor potential (TRP) channels which are expressed in primary afferent endings of free sensory neurons called nociceptors. TRP channels in nociceptors are involved in the detection of thermal, but also mechanical and chemical stimuli. Out of seven known types of temperature-sensitive TRP channels, three are responsible for detecting painful temperatures: vanilloid receptors TRPV1 (> 42 o C) and TRPV2 (> 52 o C) detect noxious heat, and ankyrin receptor TRPA1 detects noxious cold (< 17 o C). Better knowledge of TRP channel mechanisms of action is essential for understanding TRP channel functions and ultimately for the design of potential analgesics. New findings presented in this thesis clarify mechanisms of action of TRPV1 and TRPA1 receptors, focusing on camphor and voltage sensitivity of TRPV1 channels and calcium modulation of TRPA1 channels. The first topic discussed in this thesis is the mechanism of camphor sensitivity of TRPV1 receptor. Camphor is a naturally occurring substance known since time immemorial for its effective analgesic properties, yet its mechanism of action is not understood. Camphor is known to be a partial agonist of TRPV1 channel, a full agonist of TRPV3 channel, but also an inhibitor of...
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Modulatory mechanisms of nociceptive TRP channels
Maršáková, Lenka
Detection of painful stimuli in the periphery is mediated by temperature-sensitive transient receptor potential (TRP) channels which are expressed in primary afferent endings of free sensory neurons called nociceptors. TRP channels in nociceptors are involved in the detection of thermal, but also mechanical and chemical stimuli. Out of seven known types of temperature-sensitive TRP channels, three are responsible for detecting painful temperatures: vanilloid receptors TRPV1 (> 42 o C) and TRPV2 (> 52 o C) detect noxious heat, and ankyrin receptor TRPA1 detects noxious cold (< 17 o C). Better knowledge of TRP channel mechanisms of action is essential for understanding TRP channel functions and ultimately for the design of potential analgesics. New findings presented in this thesis clarify mechanisms of action of TRPV1 and TRPA1 receptors, focusing on camphor and voltage sensitivity of TRPV1 channels and calcium modulation of TRPA1 channels. The first topic discussed in this thesis is the mechanism of camphor sensitivity of TRPV1 receptor. Camphor is a naturally occurring substance known since time immemorial for its effective analgesic properties, yet its mechanism of action is not understood. Camphor is known to be a partial agonist of TRPV1 channel, a full agonist of TRPV3 channel, but also an inhibitor of...
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