{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:59:02Z","timestamp":1740139142030,"version":"3.37.3"},"reference-count":54,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["American Heart Association Career Development Award #940567"],"award-info":[{"award-number":["American Heart Association Career Development Award #940567"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL134609"],"award-info":[{"award-number":["P01 HL134609"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL141198"],"award-info":[{"award-number":["R01 HL141198"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011594","name":"PSU | Penn State College of Medicine","doi-asserted-by":"publisher","award":["INNOVQLI Fall2021"],"award-info":[{"award-number":["INNOVQLI Fall2021"]}],"id":[{"id":"10.13039\/100011594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:p>Muscle afferent nerve-activated reflex sympathetic nervous and blood pressure responses are exaggerated during exercise in peripheral artery diseases (PAD). However, the precise signaling pathways and molecular mediators responsible for these abnormal autonomic responses in PAD are poorly understood. Our previous study suggests that A-type voltage-gated K<jats:sup>+<\/jats:sup>(K<jats:sub>V<\/jats:sub>4) channels regulate the excitability in muscle dorsal root ganglion (DRG) neurons of PAD rats; however, it is still lacking regarding the effects of PAD on characteristics of K<jats:sub>V<\/jats:sub>4 currents and engagement of bradykinin (BK) subtype receptors. Thus, we examined K<jats:sub>V<\/jats:sub>4 currents in two distinct muscle DRG neurons, namely isolectin B<jats:sub>4<\/jats:sub>-positive and B<jats:sub>4<\/jats:sub>-negative (IB4+ and IB4\u2212) DRG neurons. IB4+ neurons express receptors for glial cell line-derived neurotrophic factor (GDNF), whereas IB4\u2212 DRG neurons are depending on nerve growth factors for survival. Our data showed that current density in muscle DRG neurons of PAD rats was decreased and this particularly appeared in IB4+ DRG neurons as compared with IB4\u2212 DRG neurons. We also showed that stimulation of BK B1 and B2 receptors led to a greater inhibitory effect on K<jats:sub>V<\/jats:sub>4 currents in IB4+ muscle DRG neurons and siRNA knockdown of K<jats:sub>V<\/jats:sub>4 subunit K<jats:sub>V<\/jats:sub>4.3 decreased the activity of K<jats:sub>V<\/jats:sub>4 currents in IB4+ DRG neurons. In conclusion, our data suggest that limb ischemia and\/or ischemia-induced BK inhibit activity of K<jats:sub>V<\/jats:sub>4 channels in a subpopulation of the thin fiber muscle afferent neurons depending on GDNF, which is likely a part of signaling pathways involved in the exaggerated blood pressure response during activation of muscle afferent nerves in PAD.<\/jats:p>","DOI":"10.1152\/ajpregu.00117.2022","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T14:56:30Z","timestamp":1662994590000},"page":"R616-R627","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["K<sub>V<\/sub>4 channels in isolectin B4 muscle dorsal root ganglion neurons of rats with experimental peripheral artery disease: effects of bradykinin B1 and B2 receptors"],"prefix":"10.1152","volume":"323","author":[{"given":"Qin","family":"Li","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Qin","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0513-3983","authenticated-orcid":false,"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.179"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/000331979905000502"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31821ecf61"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.03.008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8295054"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06351-6"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.01.046"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.063933"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70361-3"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/hc4401.098491"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.895292"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.05.032"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.1.429"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113730"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.cp120109"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009498"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.45.030183.001305"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.cp120110"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00956.2007"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsams.2017.02.011"},{"key":"B22","first-page":"192","volume":"7","author":"Barnett MW","year":"2007","journal-title":"Pract Neurol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1113\/JP281704"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb01143.x"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb00742.x"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-03059.1998"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80966-6"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00371.2002"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/srep16713"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.227"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01267.2004"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00338.2019"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00063.2009"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.02.003.2009"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00630.2014"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.237644"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X113119990042"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06863.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0604-07.2007"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2015.12.007"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.08.008"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1177\/1744806917750995"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20982"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00388-1"},{"key":"B45","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1016-8478(23)13797-6","volume":"16","author":"Park SY","year":"2003","journal-title":"Mol Cells"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1507"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-03-0258"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.018077"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000021603.36744.5e"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1990.69.4.1225"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1993.75.5.2061"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00926.2012"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.09.013"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90295-3"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00117.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T18:10:19Z","timestamp":1727979019000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00117.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11,1]]}},"alternative-id":["10.1152\/ajpregu.00117.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00117.2022","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"type":"print","value":"0363-6119"},{"type":"electronic","value":"1522-1490"}],"subject":[],"published":{"date-parts":[[2022,11,1]]},"assertion":[{"value":"2022-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}