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Involvement of K Ca 2.3 Channels in Relaxation of Erectile Tissue Is Altered in Type 2 Diabetic Mice
Author(s) -
Steffensen Simon Gabriel Comerma,
Mogensen Susie,
Beck Lilliana,
Simonsen Ulf
Publication year - 2017
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.31.1_supplement.991.10
Subject(s) - endocrinology , medicine , erectile dysfunction , chemistry , acetylcholine , apamin , potassium channel
Activation of endothelial small conductance calcium‐activated K + channels (K Ca 2.3 or SK3) and intermediate conductance calcium‐activated K + channels (IK or K Ca 3.1) leads to vascular relaxation. Our previous studies have shown that K Ca 2.3 down‐regulation diminishes the normal erectile function; this channel it is the most expressed K Ca channels in the endothelium of corpus cavernosum. In the present study we hypothesized that K Ca 2.3 channel function is altered in erectile tissue of type 2 diabetic animals. Materials and Methods Erectile function was measured in diabetic db/db mice was compared to heterozygous control animals. Corpus cavernosum strips were mounted for isometric tension recording and processed for qPCR or Western Blot. Results In anesthetized diabetic db/db mice erectile function was diminished compared to control animals. In isolated corpus cavernosum strips from db/db mice, concentration‐dependent contractions to noradrenaline were incremented compared to strips from control mice. Apamin, a blocker of K Ca 2 channels blocked acetylcholine relaxation in corpus cavernosum from db/db and control animals, being less effective in db/db compared to control animals. NS309 (0.5 μM), an activator of K Ca 2 and K Ca 3.1 channels, potentiated acetylcholine concentration‐dependent relaxations in corpus cavernosum from control, but this was not the case in corpus cavernosum from db/db mice. SNP relaxation was similar in corpus cavernosum from db/db and control animals. K Ca 2.3 gene and protein expression was incremented in corpus cavernosum from db/db mice, nevertheless protein expressed in the aorta was diminished. Conclusions Our results suggest that in type 2 diabetes K Ca 2.3 channel expression is down‐regulated in the systemic circulation, and upregulated in erectile tissue. In erectile tissue noradrenaline contraction is increased and the effect of NS309 reduced which may be related to impaired K Ca 2.3 channel function. These changes may contribute to impairment of erectile function in diabetes. Support or Funding Information We acknowledge Aarhus University, Novo Nordisk and Consejo de Desarrollo Cientifico y Humanistico de la Universidad Central de Venezuela (CDCH‐UCV) for their support.