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BIN1 clusters Ca V 1.2 channels in vascular smooth muscle
Author(s) -
O'Dwyer Samantha,
Moreno Claudia,
Klug Nicholas,
Santana Luis Fernando
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.827.2
Subject(s) - vascular smooth muscle , depolarization , chemistry , electrophysiology , anatomy , biophysics , smooth muscle , patch clamp , medicine , biology , endocrinology
Resistance vessel such as mesenteric arteries respond to increases in intravascular pressure by constricting. Ca 2+ influx via voltage‐gated Ca V 1.2 channels in the smooth muscle surrounding these vessels is critical for the development of myogenic tone and thus the regulation of arterial dimeter and blood flow. Our group discovered that Ca V 1.2 channels have an inherent ability to form clusters and functionally couple in response to local elevations in [Ca 2+ ] i . The consequence of these channels coming together is that they amplify Ca 2+ influx during depolarization. However, the mechanisms dictating the arrangement of Ca V 1.2 channels in smooth muscle cells are unknown. BIN1, a member of the BAR (Bin1‐Amphiphysin‐Rvs) domain superfamily, has been implicated in the trafficking of Ca V 1.2 channels but has not yet been studied in smooth muscle. In this study, we test the hypothesis that BIN1 promotes the formation of Ca V 1.2 clusters enhancing overall Ca 2+ influx into the vascular smooth muscle and shaping arterial diameter. We report that BIN1 is expressed and translated in arterial smooth muscle while ground state depletion (GSD) super‐resolution imaging suggest that smooth muscle specific down‐regulation of BIN1 diminishes Ca V 1.2 cluster formation. Using patch clamp electrophysiology and pressurized arteriography, we observed that loss of BIN1 substantially diminishes I Ca and attenuates arterial tone. Overall, these results suggest that BIN1 is a critical component in shaping Ca V 1.2 clustering and plays a physiological role in vascular smooth muscle Ca 2+ entry and arterial diameter. Support or Funding Information This work is supported by NIH R01 HL085870 (LFS), T32GM099608 (SO), and 18PRE33960249 (SO) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .