Differences in expression and function of ryanodine receptors between arteries and arterioles in the mouse

Abstract

Ryanodine receptors (RyR) in smooth muscle cells (SMC) underlie Ca2+ sparks and Ca2+‐induced‐Ca2+ release, contributing to the regulation of myogenic tone in arteries. In contrast, RyR are silent and are not involved in Ca2+ signals in SMC or myogenic tone in hamster arterioles. The purpose of the present study was to investigate the role of RyR in vessels of male C57BL/6 mice. We tested the hypothesis that differences in RyR isoform expression contribute to differences in RyR function in iliac feed arteries (FA) vs. cremaster arterioles (CA). In cannulated pressurized (80 cm H2O) vessels (34 – 37 °C), ryanodine (10 μM) constricted FA (from 53 ± 4 to 40 ± 3 μm; n = 5, p < 0.05) but not CA (24 ± 2 μm vs. 22 ± 2 μm; n = 5, p > 0.05). Transcript levels for RyR2 in freshly isolated SMC assessed by q‐RT‐PCR were 2.1 ± 0.3 ‐fold higher in FA vs. CA (n = 7, p < 0.05), while those for RyR3 were 0.6 ± 0.1 in FA vs. CA (n = 6, p < 0.05). RyR1 transcripts were not detected in SMC from FA or CA. Immunofluorescence with an anti‐RyR1/2 antibody showed clustered labeling in FA SMC (n = 6 SMC) suggestive of RyR2 expression in endoplasmic reticulum. In contrast, more uniform cytoplasmic staining in CA SMC (n = 13 SMC) suggested non‐organelle‐specific staining. These data support our hypothesis and indicate fundamental differences in SMC RyR expression and function between arteries and arterioles across rodent species. Supported by NIH HL086483 & AHA Fellowship 0815778G.