Articles: acid-sensing-ion-channels-metabolism.
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Sensory nerve fibers innervating the ocular anterior surface detect external stimuli producing innocuous and painful sensations. Protons are among the first mediators released by damaged cells during inflammation, tissue injury, or other chronic ophthalmic conditions. We studied whether acid-sensing ion channels (ASICs) are expressed in corneal sensory neurons and their roles in the response to moderate acidifications of the ocular surface and in pathologies producing ocular surface inflammation. ⋯ Our results show that, in addition to the established role of TRPV1, ASICs play a significant role in the detection of acidic insults at the ocular surface. The identification of ASICs in corneal neurons and their alterations during different diseases is critical for the understanding of sensory ocular pathophysiology. They are likely to mediate some of the discomfort sensations accompanying several ophthalmic formulations and may represent novel targets for the development of new therapeutics for ocular pathologies.
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Med Sci Sports Exerc · Feb 2015
ASIC3 contributes to the blunted muscle metaboreflex in heart failure.
During exercise, the sympathetic nervous system is activated and blood pressure and HR increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that lactic acid stimulates acid-sensing channel subtype 3 (ASIC3), inducing a neurally mediated pressor response. Thus, we hypothesized that the pressor response to ASIC3 stimulation is smaller in HF rats because of attenuation in expression and function of ASIC3 in sensory nerves. ⋯ Compared with those in controls, cardiovascular responses to lactic acid administered into the hind limb muscles are blunted in HF rats owing to attenuated ASIC3. This suggests that ASIC3 plays a role in engagement in the attenuated metaboreceptor component of the exercise pressor reflex in HF.
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The acid-sensing ion channel (ASIC) has emerged as a novel type of ion channel that is activated by extracellular protons as well as nonproton ligands. Advances in ASIC research have resolved its multifaceted structural and functional properties, including its widespread distribution, polymodal activation, and activity-dependent regulation of its expression. ⋯ Here we review the contribution of ASICs at the peripheral and central levels to the development of acute pain, inflammatory pain, neuropathic pain, and anxiety-related disorders, as well as their potential underlying mechanisms. Accumulating evidence suggests that ASICs represent a novel class of promising targets for developing effective therapies for pain and anxiety.
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In the present study we determined the role of transient receptor potential V1 channel (TRPV1) and acid-sensing ion channel 3 (ASIC3) in chronic nociception. ⋯ Data suggest that TRPV1 and ASIC3 participate in the development and maintenance of long-lasting secondary allodynia and hyperalgesia induced by formalin in rats. The use of TRPV1 and ASIC3 antagonists by peripheral administration could prove useful to treat chronic pain.
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Neuroscience letters · Nov 2014
Comparative StudyDifferences in acid-induced currents between oxytocin-mRFP1 and vasopressin-eGFP neurons isolated from the supraoptic and paraventricular nuclei of transgenic rats.
The hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) consists of two types of magnocellular neurosecretory cells, oxytocin (OXT) and arginine vasopressin (AVP). We generated and characterized rats that express an OXT-monomeric red fluorescent protein 1 (mRFP1) and an AVP-enhanced green fluorescent protein (eGFP) fusion transgene. These transgenic rats enable the visualization of OXT or AVP neurons. ⋯ The acid-induced currents of OXT-mRFP1 neurons were significantly smaller than those of AVP-eGFP neurons from the double transgenic rats. These currents were almost completely inhibited by amiloride. The difference of acid-sensitivity between OXT and AVP neurons might contribute to maintaining systematic order in hypothalamic function.