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K V 7 Channels are Potential Regulators of the Exercise Pressor Reflex
Author(s) -
Wright Andrew,
Ramachandra Renuka,
Elmslie Keith
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.837.4
Subject(s) - bradykinin , medicine , reflex , endocrinology , chemistry , neuroscience , receptor , biology
The exercise pressor reflex (EPR) is a peripheral neural reflex that originates in skeletal muscle and is activated by exercise‐induced signals to increase arterial blood pressure, ventilation, and cardiac output. Muscle ischemia can elicit the EPR, which can be inappropriately activated in patients with peripheral vascular disease and heart disease to increase the incidence of myocardial infarction. The goal of this research was to better understand the receptor/channels that control excitability of group III and group IV muscle afferent fibers that give rise to the EPR. Certain chemicals such as bradykinin are released within contracting muscle and enhance the excitability of group III/IV afferents to evoke the EPR. However, the mechanism by which bradykinin elicits the EPR is unknown. K V 7 channels strongly regulate neuronal excitability and have been shown to be modulated by bradykinin. We have identified K V currents in identified muscle afferents by their characteristic activation/deactivation kinetics and block by K V 7 specific inhibitor XE991. The K V 7 current was also inhibited by 300 nM bradykinin. A K V 7 channel antibody labeled group IV muscle afferent fibers within muscle, which demonstrated axonal expression of these channels. K V 7 likely modulates the EPR. The inhibition of K V 7 by bradykinin could be a mechanism by which this metabolic mediator enhances EPR excitability. Furthermore, our results suggest that the recently FDA approved K V 7 activator, retigabine, could be used to reduce cardiac stress resulting from the exacerbated EPR in patients with cardiovascular disease. This study is funded by NIH grant AR059397 and the ATSU‐KCOM Graduate Program Committee.