Channels
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Review Case Reports
Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review.
To verify the diagnosis of channelopathies in two families and explore the mechanism of the overlap between periodic paralysis (PP) and paramyotonia congenita (PMC). ⋯ SCN4A gene mutations can cause the overlap of PMC and PP (especially the HypoPP2). The clinical symptoms of episodic weakness and stiffness could happen at a different time or temperature. Based on diagnosis assessments such as medical history and muscle biopsy, further evaluations on long-time exercise test, genetic analysis, and patch clamp electrophysiology test need to be done in order to verify the specific subtype of channelopathies. Furthermore, the improvement of one member in the pregnancy period can be used as a reference for the other female in the child-bearing period with T704M.
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In the last 2 decades biomedical research has provided great insights into the molecular signatures underlying painful conditions. However, chronic pain still imposes substantial challenges to researchers, clinicians and patients alike. Under pathological conditions, pain therapeutics often lack efficacy and exhibit only minimal safety profiles, which can be largely attributed to the targeting of molecules with key physiological functions throughout the body. ⋯ Indeed, manipulation of such PPIs entails the modulation of ion channel activity with widespread implications for influencing nociceptive signaling in a more specific way. In this review, we highlight recent advances in modulating ion channels and receptors via their PPI networks in the pursuit of relieving chronic pain. Moreover, we critically discuss the potential of targeting PPIs for developing novel pain therapies exhibiting higher efficacy and improved safety profiles.
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Initiated by the activation of various nociceptors, pain is a reaction to specific stimulus modalities. The μ-opioid receptor (MOR) agonists, including morphine, remain the most potent analgesics to treat patients with moderate to severe pain. However, the utility of MOR agonists is limited by the adverse effects associated with the use of these drugs, including analgesic tolerance and physical dependence. ⋯ The regulation of many downstream targets of TRPV1 plays a critical role in this process, including calcitonin gene-related peptide (CGRP) and substance P (SP). Additional factors also include capsaicin treatment blocking the anti-nociception effects of morphine in rats, as well as opioid modulation of TRPV1 responses through the cAMP-dependent PKA pathway and MAPK signaling pathways. Here, we review new insights concerning the mechanism underlying MOR-TRPV1 crosstalk and signaling pathways and discuss the potential mechanisms of morphine-induced anti-nociception, tolerance and dependence associated with the TRPV1 signaling pathway and highlight how understanding these mechanisms might help find therapeutic targets for the treatment of morphine induced antinociception, tolerance and dependence.
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Voltage-gated calcium channels (VGCC) play obligatory physiological roles, including modulation of neuronal: functions, synaptic plasticity, neurotransmitter release and gene transcription. Dysregulation and maladaptive changes in VGCC expression and activities may occur in the sensory pathway under various pathological conditions that could contribute to the development of pain. In this review, we summarized the most recent findings on the regulation of VGCC expression and physiological functions in the sensory pathway, and in dysregulation and maladaptive changes of VGCC under pain-inducing conditions. The implications of: these changes in understanding the mechanisms of pain transduction and in new drug design are also discussed.
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Hemichannels are large pore ion channels that in the traditional view are formed when half a gap connexin junction opens to the extracellular space. It is now evident that other ion channel families, including the newly discovered pannexin family can form channels with all the nascent properties of hemichannels. ⋯ Additionally, pannexin-1 appears to play a role in neuronal death. Hemichannels form a novel and unique class of ion channels that likely have diverse physiological and pathophysiological roles in the nervous system.