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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,
Fais Rafael Sobrano,
Beck Lilliana,
Mogensen Susie,
Simonsen Ulf
Publication year - 2019
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.2019.33.1_supplement.512.7
Subject(s) - endocrinology , erectile dysfunction , medicine , apamin , chemistry , acetylcholine , potassium channel , calcium channel blocker , calcium
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 erectile function; this channel it is the most expressed K Ca channel 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 and was compared to heterozygous control animals. Corpus cavernosum strips were mounted for isometric tension recording, and they were processed for qPCR or Western Blot. The current research was performed in accordance to FASEB Statement of Principles for the use of Animal in Research and Education. Results In anesthetized diabetic db/db mice erectile function was diminished compared to control animals. Concentration‐dependent contractions to noradrenaline were increased in corpus cavernosum strips from db/db compared to strips from control mice. Apamin, a blocker of K Ca 2 channels inhibited 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 concentration‐response curves for acetylcholine 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 increased in corpus cavernosum from db/db mice, nevertheless protein expressed in aorta was unchanged. Conclusions Our results suggest that in type 2 diabetes K Ca 2.3 channel expression is unchanged 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 Aarhus University, Novo Nordisk Foundation and the Danish Research Council. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .