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Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons.
J Neurophysiol. 2013 Jul; 110(2):408-17.JN

Abstract

Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.

Authors+Show Affiliations

Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23636721

Citation

Dang, Khoa, et al. "Cyclophosphamide-induced Cystitis Reduces ASIC Channel but Enhances TRPV1 Receptor Function in Rat Bladder Sensory Neurons." Journal of Neurophysiology, vol. 110, no. 2, 2013, pp. 408-17.
Dang K, Bielefeldt K, Gebhart GF. Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons. J Neurophysiol. 2013;110(2):408-17.
Dang, K., Bielefeldt, K., & Gebhart, G. F. (2013). Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons. Journal of Neurophysiology, 110(2), 408-17. https://doi.org/10.1152/jn.00945.2012
Dang K, Bielefeldt K, Gebhart GF. Cyclophosphamide-induced Cystitis Reduces ASIC Channel but Enhances TRPV1 Receptor Function in Rat Bladder Sensory Neurons. J Neurophysiol. 2013;110(2):408-17. PubMed PMID: 23636721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons. AU - Dang,Khoa, AU - Bielefeldt,Klaus, AU - Gebhart,G F, Y1 - 2013/05/01/ PY - 2013/5/3/entrez PY - 2013/5/3/pubmed PY - 2014/1/30/medline KW - ASIC KW - TRPV1 receptors KW - acid KW - bladder sensory neurons KW - capsaicin KW - cyclophosphamide KW - cystitis KW - pH KW - proton KW - visceral hypersensitivity KW - whole cell patch clamp SP - 408 EP - 17 JF - Journal of neurophysiology JO - J Neurophysiol VL - 110 IS - 2 N2 - Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/23636721/Cyclophosphamide_induced_cystitis_reduces_ASIC_channel_but_enhances_TRPV1_receptor_function_in_rat_bladder_sensory_neurons_ L2 - https://journals.physiology.org/doi/10.1152/jn.00945.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -