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Effects of bradykinin on voltage‐gated K V 4 channels in muscle dorsal root ganglion neurons of rats with experimental peripheral artery disease
Author(s) -
Li Qin,
Qin Lu,
Li Jianhua
Publication year - 2021
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp281704
Subject(s) - dorsal root ganglion , medicine , reflex , femoral artery , bradykinin , anatomy , endocrinology , hindlimb , neuroscience , biology , dorsum , receptor
Key points During exercise, bradykinin (BK), a muscle metabolite in ischaemic muscles, exaggerates autonomic responses to activation of muscle afferent nerves in peripheral artery disease (PAD). We examined whether BK inhibits activity of K V 4 channels in muscle afferent neurons of PAD rats induced by femoral artery occlusion. We demonstrated that: 1) femoral occlusion attenuates K V 4 currents in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles and decreases the threshold of action potential firing; 2) BK has a greater inhibitory effect on K V 4 currents in muscle DRG neurons of PAD rats; and 3) expression of K V 4.3 is downregulated in DRGs of PAD rats and inhibition of K V 4.3 significantly decreases activity of K V 4 currents in muscle DRG neurons. Femoral artery occlusion‐induced limb ischaemia and/or ischaemia‐induced metabolites (i.e. BK) inhibit activity of K V 4 channels in muscle afferent neurons and this is likely involved in the exaggerated exercise pressor reflex in PAD.Abstract Muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses are exaggerated during exercise in patients with peripheral artery diseases (PAD) and in PAD rats induced by femoral artery occlusion. However, the precise signalling pathways and molecular mediators responsible for these abnormal autonomic responses in PAD are poorly understood. A‐type voltage‐gated K + (K V ) channels are quintessential regulators of cellular excitability in the various tissues. Among K V channels, K V 4 (i.e. K V 4.1 and K V 4.3) in primary sensory neurons mainly participate in physiological functions in regulation of mechanical and chemical sensation. However, little is known about the role of K V 4 in regulating neuronal activity in muscle afferent neurons of PAD. In addition, bradykinin (BK) is considered as a muscle metabolite contributing to the exaggerated exercise pressor reflex in PAD rats with femoral artery occlusion. Our data demonstrated that: 1) K V 4 currents are attenuated in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles of PAD rats, along with a decreasing threshold of action potential firing; 2) K V 4 currents are inhibited by application of BK onto muscle DRG neurons of PAD rats to a greater degree; and 3) expression of K V 4.3 is downregulated in the DRGs of PAD rats and K V 4.3 channel is a major contributor to the activity of K V 4 currents in muscle DRG neurons. In conclusion, data suggest that femoral artery occlusion‐induced limb ischaemia and/or ischaemia‐induced metabolites (i.e. BK) inhibit the activity of K V 4 channels in muscle afferent neurons likely leading to the exaggerated exercise pressor reflex observed in PAD.