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Nanoscale‐Organization of Key Molecular Complexes Differentially Alter Vascular Smooth Muscle Function in Male and Females
Author(s) -
Matsumoto Collin,
Tajada Sendoa,
Santana Luis Fernando
Publication year - 2020
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.2020.34.s1.07617
Subject(s) - vascular smooth muscle , sarcolemma , angiotensin ii , protein kinase c , receptor , medicine , endocrinology , myocyte , contraction (grammar) , diacylglycerol kinase , microbiology and biotechnology , endoplasmic reticulum , muscle contraction , chemistry , depolarization , biology , signal transduction , smooth muscle
Arterial smooth muscle contraction is the result of both electro‐mechanical and pharmaco‐mechanical coupling. During electro‐mechanical coupling, membrane depolarization activates dihydropyridine‐sensitive Ca V 1.2 channels, raising intracellular calcium concentrations ([Ca 2+ ] i ) and results in contraction of arterial smooth muscle. Pharmaco‐mechanical coupling activation of G‐protein coupled receptors (GPRCs) by angiotensin II (AngII) produces inositol 1,4,5‐triphosphate (IP3) and protein kinase C (PKC) activated diacylglycerol (DAG). This leads to an increase in [Ca 2+ ] i via sarcoplasmic reticulum IP3 receptors and PKC dependent Ca 2+ channels in the sarcolemma. It is known that male and females respond differently to antihypertensive drugs. However, it is unknown whether the nano‐scale organization of key molecular complexes between sexes play a role in smooth muscle physiology. Our data show that Ca 2+ influx through Ca V 1.2 channels is larger in female than in male arterial myocytes. Furthermore, male smooth muscle responds greater to GPCR activation by AngII than female. We observed sex‐specific nano‐organization of Ca V 1.2 and AngII related signaling proteins angiotensin II receptor type 1 (AngIIR1), AKAP150 and PKC in arterial smooth muscle. We propose that there are sex‐based differences in smooth muscle physiology that are a result of different nano‐organization of signaling complexes. Support or Funding Information T32 HL086350