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Potassium Channel Dysfunction in Dorsal Root Ganglia Contributes to the Exaggerated Exercise Pressor Reflex in Heart Failure
Author(s) -
Wang Hanjun,
Rozanski George,
Zucker Irving
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.827.1
Subject(s) - microinjection , reflex , medicine , endocrinology , potassium channel , heart failure , anesthesia , chemistry
An exaggerated exercise pressor reflex (EPR) causes excessive sympatho‐excitation and exercise intolerance in the chronic heart failure (CHF) state. A previous study from this laboratory demonstrated that peripheral sensitization of the afferent limb (mainly mechanically sensitive fibers) is an important contributor to the exaggerated EPR in CHF. Considering that voltage‐gated potassium (Kv) channels critically regulate afferent neuronal excitability, we examined the potential role of Kv channels in mediating the sensitized EPR in CHF. Our data demonstrate that microinjection of a Kv channel blocker, 4‐aminopyridine (4‐AP, 10 mM/100nl), into lumbar L4/L5 dorsal root ganglia (DRGs) enhances the pressor response to either static contraction (EPR, 14.0±2.6 vs. 25.8±2.8 mmHg, P <0.05) or passive stretch (mechanoreflex, 12.5±2.5 vs. 22.1±2.7 mmHg, P <0.05) in sham rats whereas this treatment has no effect on the EPR and mechanoreflex in CHF rats (EPR, 28.8±3.2 vs. 31.3±3.0 mmHg; Stretch, 25.6±2.9 vs. 28.3±2.7 mmHg). Furthermore, molecular data show that multiple Kv channel isoforms (Kv1.4, Kv3.4, Kv4.2 and Kv4.2)were downregulated in lumbar DRGs of CHF rats compared to sham rats. Finally, data from patch clamp experiments demonstrate that the total Kv current, especially I A , was dramatically decreased in medium‐sized muscle afferent neurons (mainly Adetla neurons) from CHF rats compared to sham rats, indicating a functional loss of Kv channels in muscle afferent A delta neurons. These data suggest that Kv channel dysfunction in DRGs play a critical role in mediating the exaggerated EPR and afferent sensitization in CHF.