Subpopulations of Rat Vascular Smooth Muscle Cells as Discriminated by Calcium Release Mechanisms From Internal Stores

• Published in: Circulation research 1991-08, Vol.69 (2), p.551-556
• Main Authors: Shin, Wee Soo, Toyo-oka, Teruhiko, Masuo, Masatoshi, Okai, Yoko, Fujita, Hideo, Sugimoto, Tsuneaki
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Caffeine - pharmacology; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Cells, Cultured; Cytosol - metabolism; Image Processing, Computer-Assisted; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Rats; Rats, Inbred Strains; Sarcoplasmic Reticulum - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.69.2.551

Transsarcolemmal influx and release from the sarcoplasmic reticulum (SR) through specific Ca channels are the two main pathways to elevate cytosolic Ca (Cai) in vascular smooth muscle cells (VSMCs). To elucidate intercellular distribution and function of the Ca channel in SR in cultured VSMCs, we observed Cai transients by digital two-dimensional imaging with a fluorescent Ca indicator, fura-2, and found an alternative response to either caffeine or angiotensin II under the condition that selectively enabled Ca release from SR. Caffeine (20 mM) increased the Cai by 292±36% (mean±SEM) over the basal level in one third of the VSMC population (n=19), while the remaining cells in the same observation field showed no or very weak response (110±4%). In contrast, after the treatment with caffeine plus ryanodine (30 μM), which inactivates the caffeine-sensitive channel, and with 1 mM Ca chelator (EGTA) instead of Ca in the incubation medium to block the Ca entry from outside, angiotensin II (10 nM) induced the Cai elevation (287±26%) in previously caffeine-nonresponsive cells, although caffeine-responsive cells retained quiescence (112±2%). These responses did not differ when the order of the reagent application was reversed. These heterogeneities of VSMCs in the Cai response to vasoactive substances indicate that VSMCs are functionally divided into subgroups with different Ca channel predominance on SR, necessitating reevaluation of the previous studies obtained from multiple VSMCs. (Circulation Research 1991;69:551-556)