Smooth muscle cells respond to InsP3-generating (sarcolemma-acting) neurotransmitters and hormones by releasing Ca2+ from the internal store. However, the release of Ca2+ does not occur uniformly throughout the cytoplasm but often into a localized area before being transmitted to other regions of the cell in the form of Ca2+ waves and oscillations to actively spread information within and between cells. Yet, despite their significance, our understanding of the generation of oscillations to waves is incomplete. A major aspect of controversy centres on whether or not Ca2+ released from the InsP3 receptor activates RyRs (ryanodine receptors) to generate further release by Ca2+-induced Ca2+ release and propagate waves or whether the entire process arises from InsP3 receptor activity alone. Under normal physiological conditions the [Ca2+] required to activate RyR (approx. 15 μM) exceeds the bulk average [Ca2+]c (cytoplasmic Ca2+ concentration) generated by InsP3 receptor activity (<1 μM). Progression of waves and oscillations by RyR activity would require a loss of control of RyR activity and an unrestrained positive feedback on Ca2+ release. Under store-overload conditions, RyR Ca2+ sensitivity is increased and this enables waves to be induced by RyR activity. However, the relevance of these Ca2+-release events to normal physiological functioning is unclear. The InsP3 receptor, on the other hand, is activated by Ca2+ over the physiological range (up to 300 nM) and deactivated by higher [Ca2+]c (>300 nM), features that favour intermittent activity of the receptor as occurs in waves and oscillations. Experimental evidence for the involvement of RyR relies mainly on pharmacological approaches in the intact cell where poor drug specificity could have led to ambiguous results. In this brief review the possible interactions between InsP3 receptors and RyR in the generation of oscillations and waves will be discussed. Evidence is presented that RyRs are not required for InsP3-mediated Ca2+ transients. Notwithstanding, ryanodine can inhibit InsP3-mediated Ca2+ responses after RyR activity has been induced by caffeine or by steady depolarization which evokes spontaneous transient outward currents (a sarcolemmal manifestation of RyR activity). Ryanodine inhibits InsP3-mediated Ca2+ transients by depleting the store of Ca2+ rather than by RyR involvement in the InsP3-mediated Ca2+ increase.
Skip Nav Destination
Article navigation
October 2003
- PDF Icon PDF LinkFront Matter
Conference Article|
October 01 2003
Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle
J.G. McCarron;
J.G. McCarron
1
Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
1To whom correspondence should be addressed (e-mail J.McCarron@bio.gla.ac.uk).
Search for other works by this author on:
K.N. Bradley;
K.N. Bradley
Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Search for other works by this author on:
D. MacMillan;
D. MacMillan
Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Search for other works by this author on:
T.C. Muir
T.C. Muir
Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (5): 920–924.
Citation
J.G. McCarron, K.N. Bradley, D. MacMillan, T.C. Muir; Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle. Biochem Soc Trans 1 October 2003; 31 (5): 920–924. doi: https://doi.org/10.1042/bst0310920
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.