TY - CHAP
T1 - Nanojunctions of the Sarcoplasmic Reticulum Deliver Site- and Function-specific Calcium Signalling in Vascular Smooth Muscles
AU - Evans, Anthony
PY - 2017/2/15
Y1 - 2017/2/15
N2 - Vasoactive agents may induce myocyte contraction, dilation, and the switch from a contractile to a migratory–proliferative phenotype(s), which requires changes in gene expression. These processes are directed, in part, by Ca2 + signals, but how different Ca2 + signals are generated to select each function is enigmatic. We have previously proposed that the strategic positioning of Ca2 + pumps and release channels at membrane–membrane junctions of the sarcoplasmic reticulum (SR) demarcates cytoplasmic nanodomains, within which site- and function-specific Ca2 + signals arise. This chapter will describe how nanojunctions of the SR may: (1) define cytoplasmic nanospaces about the plasma membrane, mitochondria, contractile myofilaments, lysosomes, and the nucleus; (2) provide for functional segregation by restricting passive diffusion and by coordinating active ion transfer within a given nanospace via resident Ca2 + pumps and release channels; (3) select for contraction, relaxation, and/or changes in gene expression; and (4) facilitate the switch in myocyte phenotype through junctional reorganization. This should serve to highlight the need for further exploration of cellular nanojunctions and the mechanisms by which they operate, that will undoubtedly open up new therapeutic horizons.
AB - Vasoactive agents may induce myocyte contraction, dilation, and the switch from a contractile to a migratory–proliferative phenotype(s), which requires changes in gene expression. These processes are directed, in part, by Ca2 + signals, but how different Ca2 + signals are generated to select each function is enigmatic. We have previously proposed that the strategic positioning of Ca2 + pumps and release channels at membrane–membrane junctions of the sarcoplasmic reticulum (SR) demarcates cytoplasmic nanodomains, within which site- and function-specific Ca2 + signals arise. This chapter will describe how nanojunctions of the SR may: (1) define cytoplasmic nanospaces about the plasma membrane, mitochondria, contractile myofilaments, lysosomes, and the nucleus; (2) provide for functional segregation by restricting passive diffusion and by coordinating active ion transfer within a given nanospace via resident Ca2 + pumps and release channels; (3) select for contraction, relaxation, and/or changes in gene expression; and (4) facilitate the switch in myocyte phenotype through junctional reorganization. This should serve to highlight the need for further exploration of cellular nanojunctions and the mechanisms by which they operate, that will undoubtedly open up new therapeutic horizons.
U2 - 10.1016/bs.apha.2016.10.001
DO - 10.1016/bs.apha.2016.10.001
M3 - Chapter (peer-reviewed)
SN - 9780128114858
VL - 78
T3 - Advances in Pharmacology
SP - 1
EP - 47
BT - Vascular Pharmacology
A2 - Khalil, Raouf A.
PB - Advances in Pharmacology
CY - Cambridge, MA
ER -