Experimental Physiology最新文献

{"title":"Neuromuscular and neuromechanical assessments of respiratory performance in the mdx mouse model of Duchenne muscular dystrophy across the natural history of disease.","authors":"Michael N Maxwell, Christopher G Wilson, Mai K Elmallah, Federica Trucco, Ken D O'Halloran","doi":"10.1113/EP093392","DOIUrl":"10.1113/EP093392","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a severe life-limiting X-linked neuromuscular disorder characterised by progressive skeletal muscle degeneration and respiratory failure. The mdx mouse, lacking dystrophin, is the most widely used preclinical model of DMD, yet the trajectory of respiratory dysfunction in this model remains incompletely defined. We evaluated neural respiratory drive (NRD), neuromechanical efficiency (NME), tension-time index (TTI), inspiratory drive rate and electromyographic (EMG) frequency spectrum parameters in the diaphragm, external intercostal and parasternal muscles across the natural history of disease (aged 1-16 months). Despite early and persistent reductions in EMG activity and frequency spectrum parameters in mdx mice, NRD and TTI in respiratory muscles were largely equivalent to controls. NME was paradoxically increased in mdx mice, likely reflecting compensatory recruitment of accessory muscles rather than improved contractile efficiency of the major inspiratory muscles of breathing. The area under the pressure-time curve during sustained tracheal occlusion was reduced in mdx mice at 1 month of age but was equivalent to wild-type values at all other ages, demonstrating robust compensation even in advanced disease. No significant differences in inspiratory duty cycle, respiratory muscle effort or TTI were observed across groups. We conclude that assessments of integrative respiratory morbidity in mdx mice should focus on animals aged ≥16 months or alternative models with accelerated disease progression. Our results underscore the need for refined translational models and highlight the importance of integrating EMG-based indices for early detection and monitoring of respiratory compromise in DMD.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2279-2307"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon monoxide to 'simulate altitude': The ethical grenade.","authors":"Raphael Faiss, Franck Brocherie","doi":"10.1113/EP093704","DOIUrl":"10.1113/EP093704","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2387-2388"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of live-high, train-low strategy induced by chronic low-dose carbon monoxide exposure on haematological parameters and performance in trained individuals.","authors":"Simone Villanova, Simone Porcelli, Lena Ekström, Daniele A Cardinale","doi":"10.1113/EP093005","DOIUrl":"10.1113/EP093005","url":null,"abstract":"<p><p>Altitude training enhances haematological adaptations and endurance at sea level, typically requiring exposure to ∼2500 m altitude for 3-4 weeks. Emerging evidence suggests that low-dose carbon monoxide (CO) inhalation might mimic hypoxia and might be used by elite athletes. In this study, we examine whether periodic low-dose CO exposure can replicate the live-high, train-low model in well-trained individuals, focusing primarily on haematological and performance effects of CO exposure, with haematological markers commonly used to interpret haemoglobin mass changes discussed as exploratory. Eight well-trained individuals (four males and four females) participated in a randomized crossover study. They completed two training blocks of 4 weeks at sea level: one with CO inhalation (INCO) to simulate live-high, train-low and one with ambient air as a control (AIR), separated by a 6 month washout. Haematological variables, in vivo muscle oxidative capacity and performance metrics were assessed before and after each intervention. After INCO, haemoglobin mass (p = 0.018; +53.6 ± 10.8 g. vs. +0.8 ± 11.8 g), red blood cell volume (p = 0.032; +156.6 ± 66.7 mL vs. -65.1 ± 50.7 mL) and blood volume (p = 0.036; +240.4 ± 120.5 mL vs. -208.3 ± 167.5 mL) increased significantly compared with AIR. INCO significantly reduced immature reticulocytes (p = 0.04), but muscle oxidative capacity and performance metrics remained unchanged. These findings suggest that daily low-dose CO exposure at sea level over 4 weeks enhanced haematological adaptations more than standard training but did not affect muscle oxidative capacity or performance.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"1891-1903"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do auditory deviants evoke cortical state changes under anaesthesia? A proof-of-concept study.","authors":"Laura H Bohórquez, Manuel S Malmierca, Adam Hockley","doi":"10.1113/EP093378","DOIUrl":"10.1113/EP093378","url":null,"abstract":"<p><p>Context-dependent sensory processing within the predictive coding framework relies on detecting mismatches between incoming stimuli and internal predictive models. Sensory deviants elicit prediction errors, seen as enhanced neural responses, that update these models and influence attention and behaviour. Although prediction errors have been widely observed across brain regions, the downstream processes remain poorly understood. In this study, we recorded electrocorticography in five urethane-anaesthetised rats and identified cortical slow oscillations, characterised by spontaneous transitions between 'Up' and 'Down' states. Deviant stimuli in an auditory oddball paradigm evoked an initial positive prediction error, followed by a prolonged, all-or-nothing response which spread in a travelling wave across the cortex. Identified as putative evoked cortical Up states, these responses were not evoked by standards, omissions or a many-standards control. Up states following deviants occurred more recently after a previous Up state when compared to spontaneous Up states. In preliminary data from an awake rat, long-latency Up states were not present spontaneously or evoked. In a different rat, anaesthetic depth was key to spontaneous and evoked Up states, with more robust Up/Down states and more reliable triggering of Up states under deeper anaesthesia. These results suggest that sensory deviants may cause shifts in cortical state under anaesthesia, explaining the long-latency mismatch response under anaesthesia and sleep.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2148-2162"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effects of a glucose-fructose bar, glucose-fructose hydrogel and maltodextrin gel on carbohydrate oxidation and sprint performance in Tier 2 athletes.","authors":"Ewan Dean, Ash Osborne, Daren Subar, Paul Hendrickse, Christopher J Gaffney","doi":"10.1113/EP093136","DOIUrl":"10.1113/EP093136","url":null,"abstract":"<p><p>Carbohydrate supplementation optimises athletic performance, but the metabolic and performance impacts of commercial products/compositions are underexplored. We compared the efficacy of three commercial carbohydrate supplements: a glucose-fructose bar (GF-Bar), a glucose-fructose hydrogel (GF-Gel) and a maltodextrin-based gel (MD-Gel). Antegrade venous blood samples for glucose and insulin were measured alongside substrate utilisation in healthy Tier 2 athletes after ingesting 45 g of carbohydrates from the GF-Bar, GF-Gel and MD-Gel during a modified 1-h oral glucose tolerance test (OGTT). Additionally, the effect of supplementation on high-intensity interval exercise was evaluated during repeated maximal sprint performance. During the OGTT, the GF-Bar elicited greater total carbohydrate oxidation than MD-Gel (24.6 ± 7.4 g vs. 17.8 ± 8.6 g, P = 0.038) but not GF-Gel (20.1 ± 6.4 g, P > 0.05). Carbohydrate oxidation per minute varied over time (P < 0.001) and between products (P = 0.043), with GF-Bar (0.27 ± 0.05 g min^-1) showing higher oxidation than GF-Gel (0.21 ± 0.05 g min^-1) and MD-Gel (0.19 ± 0.06 g min^-1). No differences were observed in glucose peak, time to peak glucose or insulin concentration (P > 0.05). Peak power (P = 0.011), mean power (P < 0.001) and total work varied across sprints (P < 0.001) but not between products (P > 0.05). Perceived exertion and gastrointestinal discomfort were similar between products (P > 0.05). Despite differences in carbohydrate oxidation during the OGTT, the GF-Bar, GF-Gel and MD-Gel displayed similar metabolic and sprint performance outcomes, suggesting that, within this study, carbohydrate formulation did not impact short-duration maximal exercise.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"1831-1846"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of prolyl hydroxylase inhibitors during reperfusion in myocardial infarction: A study using cardiosphere-derived cells.","authors":"Luca Salhöfer, Ulrike B Hendgen-Cotta, Joachim Fandrey, Timm Schreiber, Tristan Leu","doi":"10.1113/EP093391","DOIUrl":"10.1113/EP093391","url":null,"abstract":"<p><p>Cardiosphere-derived cells (CDCs) are a promising in vitro model for studying myocardial ischaemia-reperfusion (I-R) injury and testing potential therapeutic interventions. This study investigated the suitability of CDCs as a model for myocardial infarction (MI) and the effects of prolyl hydroxylase inhibitor (PHI) administration during reperfusion. CDCs were generated from neonatal mouse hearts and characterized by immunofluorescence, revealing a heterogeneous mixture of cardiomyocytes, smooth muscle cells, endothelial cells, and stem cells. The CDCs were subjected to oxygen-glucose deprivation (OGD) followed by reperfusion with or without the PHI dimethyloxalylglycine (DMOG). Cell viability, hypoxia-inducible factor 1-alpha (HIF-1α) accumulation, and gene expression were analysed. The results showed that DMOG administration during reperfusion reduced lactate dehydrogenase release, indicating decreased cell death. HIF-1α protein levels increased during OGD and were further stabilized by DMOG during reperfusion. The expression of HIF-1α target genes, such as vascular endothelial growth factor (Vegfa), and genes involved in regeneration and cardiac function, including connective tissue growth factor (Ctgf), cyclin D2 (Ccnd2), and beta-1 adrenergic receptor (Adrb1), was modulated by OGD and DMOG treatment. Comparisons with an in vivo mouse I-R injury model revealed similarities in gene expression patterns. In conclusion, CDCs serve as an effective in vitro model for studying I-R injury, closely resembling the in vivo situation. Furthermore, PHI administration during reperfusion reduces cell death and modulates the expression of genes involved in cardioprotection and regeneration, highlighting the potential of PHIs as a therapeutic strategy for I-R injury.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2058-2072"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory effects of cathelicidin in the gut-brain axis: A novel link between mucosal immunity and neuroinflammation.","authors":"Mehrdad Nourizadeh, Amir Arsalan Ghahari, Ehsan Zandi, Seyedeh Zeynab Rasouli, Shaghayegh Davari, Mobina Hoseinzadeh, Mir Alireza Nourazar","doi":"10.1113/EP093221","DOIUrl":"10.1113/EP093221","url":null,"abstract":"<p><p>Cathelicidins are evolutionarily conserved host defence peptides known for their dual antimicrobial and immunomodulatory functions. Among them, LL-37 in humans and CRAMP in rodents have emerged as crucial regulators of both mucosal immunity and CNS inflammation. This review explores the emerging evidence that positions cathelicidins as key modulators of the gut-brain axis, a bidirectional communication network increasingly implicated in neuroinflammatory and neurodegenerative disorders. Drawing on a diverse body of animal and human research, we examine the multifaceted roles of cathelicidin in maintaining intestinal barrier integrity, shaping microbiota composition and regulating innate immune signalling. Particular attention is paid to how gut-derived metabolites, such as short-chain fatty acids and vitamin D, influence cathelicidin expression, with downstream consequences for both gastrointestinal and neural health. In the CNS, cathelicidin exhibits context-dependent effects, acting as a neuroprotective modulator when derived from neurons, but exacerbating glial-mediated inflammation when sourced from peripheral immune cells. This functional dichotomy underscores the importance of cellular origin, concentration and microenvironmental cues. Furthermore, we delineate how cathelicidin facilitates crosstalk between peripheral and central compartments, serving as both a local effector and a systemic messenger. Collectively, these insights support a reconceptualization of cathelicidin not merely as a passive antimicrobial peptide, but as an active molecular bridge between mucosal immunity and neuroinflammation, with promising implications for diagnostics and therapeutics targeting dysfunction of the gut-brain axis.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"1733-1745"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of hypoxia on muscle activation at equivalent absolute and relative intensity during incremental and constant load exercise to task failure.","authors":"Dania Ibrahim, Youmna Elsayed Hassanein, Nathan E Townsend","doi":"10.1113/EP093320","DOIUrl":"10.1113/EP093320","url":null,"abstract":"<p><p>We examined the impact of moderate hypoxia (HYPO) on muscle activation during incremental exercise matched for both absolute and equivalent relative intensity. Fifteen active subjects (10 males, 5 females) completed two ramp incremental test and two step tests in normoxia (NORM; <math> <semantics><msub><mi>F</mi> <mrow><mi>i</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${F_{{mathrm{i}}{{mathrm{O}}_2}}}$</annotation></semantics> </math>  = 0.209) and HYPO ( <math> <semantics><msub><mi>F</mi> <mrow><mi>i</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${F_{{mathrm{i}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> ≈ 0.135) in counterbalanced order. The respiratory compensation point (RCP) determined from ramp testing was used to normalize relative intensity during step testing, which included a final stage to task failure (TF) above RCP. Electromyography (EMG) was recorded for rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM), and normalized to a pre-test maximal sprint effort. Linear mixed modelling was used to examine fixed effects of condition (NORM, HYPO) and intensity (absolute, relative) on EMG activity. During the ramp test, HYPO significantly reduced <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${dot V_{{{mathrm{O}}_2}{mathrm{peak}}}}$</annotation></semantics> </math> (∼13%), PPO (∼15%), and power at RCP (∼16%). EMG breakpoints occurred at lower absolute intensity in HYPO for RF and VL. When matched for relative intensity, muscle activity was lower in HYPO for VM and VL, but not RF. EMG activity at TF revealed a similar pattern whereby a strong association to absolute power was present regardless of test protocol or <math> <semantics><msub><mi>F</mi> <mrow><mi>i</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${F_{{mathrm{i}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> . These results suggest that altered relative metabolic stress has a negligible impact on muscle activation at work rates below the RCP. For exercise in the severe domain our data aligns with the theory that muscle activation is not critically regulated to a given level at TF, but appears to be task-specific and independent of oxygen availability.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"1933-1947"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postural control in humans: a study using transcutaneous spinal cord stimulation.","authors":"Natalia Shamantseva, Ivan Sakun, Tatiana Klishkovskaia, Andrey Aksenov, Vsevolod Lyakhovetskii, Tatiana Moshonkina","doi":"10.1113/EP093385","DOIUrl":"10.1113/EP093385","url":null,"abstract":"<p><p>The aim of the study was to investigate the spinal mechanisms involved in regulating postural balance in humans. Participants stood in a normal stance, with their spinal postural networks either non-invasively activated or not stimulated by electrical stimulation. Postural sway, muscle activity, joint kinematics and respiratory movements were monitored. Half of the participants depended on external sensory cues for controlling balance (field dependent), whereas the other half did not (field independent). Stimulation was performed at the T11-T12 or L1-L2 vertebral level using intensities below the motor threshold. When participants stood without stimulation, differences in body segment movement in the frontal plane were observed between subgroups, in addition to similarities in segment movement in the sagittal plane. Field-dependent participants demonstrated greater mediolateral sway and pelvic motion and relied more on hip involvement in frontal centre of pressure dynamics than field-independent participants. Stimulation at T11-T12 induced changes in muscle activity and body segment coordination in both groups. It led to a reduction in mediolateral sway and enhanced postural stability, but only in field-dependent individuals. Stimulation at L1-L2 altered muscle activity and joint kinematics in both subgroups without having an effect on postural stability. Stimulation did not affect respiratory movements or posture-respiratory coupling. In the human spinal cord, the interneuronal networks involved in postural regulation are located at the T11-T12 level and operate under supraspinal control. Interneuronal networks at the L1-L2 level also modulate muscle activity and body segment coordination; however, their specific role in regulating upright posture remains unclear.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2163-2175"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA_B receptor-mediated modulation of sensory neuron excitability: Roles of Ca_V2.2, G-protein-coupled inwardly rectifying potassium (GIRK) channels, and hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels in human and mouse nociception.","authors":"Mariana Brizuela, Anuja R Bony, Sonia Garcia-Caraballo, David J Adams, Stuart M Brierley","doi":"10.1113/EP093318","DOIUrl":"10.1113/EP093318","url":null,"abstract":"<p><p>Chronic visceral pain is a key symptom of irritable bowel syndrome. Modulation of voltage-gated calcium and potassium channels by G protein-coupled receptors plays a key role in dampening nociceptive transmission. Both baclofen and the analgesic peptide α-conotoxin Vc1.1 activate GABA_B receptors (GABA_BR), resulting in inhibition of Ca_V2.2 and Ca_V2.3 calcium channels to reduce colonic nociception. Recent studies have also shown that GABA_BR activation potentiates G-protein-coupled inwardly rectifying potassium (GIRK)-1/2 channels in mammalian sensory afferent neurons. In this study, we investigated the expression of these ion channel targets in rodent and human dorsal root ganglion (DRG) neurons, including those innervating the colon. We examined how Ca_V2.2 and GIRK channel antagonists, as well as a GIRK channel activator, influence the passive and active electrical properties of adult mouse DRG neurons. We also assessed the effects of α-conotoxin Vc1.1 on neuronal excitability in the presence of the selective Ca_V2.2 antagonist ω-conotoxin CVIE and the GIRK channel activator ML297. We further evaluated the impact of the GIRK channel antagonist tertiapin-Q on excitability in mouse colonic DRGs and afferents and explored the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Our findings demonstrate that both Ca_V2.2 inhibition and GIRK channel potentiation reduce excitability in mouse DRGs, likely mediating the antinociceptive effects of Vc1.1 and baclofen observed in vivo. However, GIRK channel potentiation appears to play only a limited role in modulating excitability in colon-innervating DRGs and colonic afferents. These findings suggest that neurons innervating different body regions use distinct mechanisms to regulate excitability and nociceptive signalling.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"2026-2043"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}