IP3-mediated Ca2+ release regulates atrial Ca2+ transients and pacemaker function by stimulation of adenylyl cyclases

NEW & NOTEWORTHY This study provides evidence supporting the proposal that IP3 signaling in cardiac atria and sinoatrial node involves stimulation of Ca2 þ -activated adenylyl cyclases by IP3-evoked Ca2 þ release from junctional sarcoplasmic reticulum

Rebecca A. Capel; Samuel J. Bose; Thomas P. Collins; Skanda Rajasundaram; Thamali Ayagama; Manuela Zaccolo; Rebecca-Ann Beatrice Burton; Derek A. Terrar

2020

Scholarcy highlights

  • Submitted 20 May 2020 / Revised 12 October 2020 / Accepted 14 October 2020 http://www.ajpheart.org H95Published by the American Physiological Society
  • NEW & NOTEWORTHY This study provides evidence supporting the proposal that IP3 signaling in cardiac atria and sinoatrial node involves stimulation of Ca2 þ -activated adenylyl cyclases by IP3-evoked Ca2 þ release from junctional sarcoplasmic reticulum
  • Type 2 IP3 Receptors are Colocalized with AC8 in Cardiac Atrial Myocytes
  • Pixel-by-pixel analysis revealed substantial colocalization between AC8 and IP3R type 2 in isolated guinea pig atrial myocytes, Pearson’s overlap coefficient R = 0.81 ± 0.02, representative cell shown in Fig. 1, E–G
  • Our work is consistent with the hypothesis that interaction of IP3-mediated Ca2 þ release with the cAMP system is essential for the positive inotropic and chronotropic effects of this compound in the cardiac atria and sinoatrial node, and that this is physiologically important in the response of these tissues to a-adrenoceptor stimulation
  • In the presence of H89, photorelease of IP3 had no significant effect on maximum upstroke velocity or time to 50% recovery, time to 90% recovery was significantly reduced, though to a lesser extent than the effects seen after exposure to IP3 under control conditions
  • We agree that cAMP and protein kinase A are central to the response of atrial myocytes and the sinoatrial node to PE, and IP3, we did not find evidence that nitric oxide or soluble guanylyl cyclase activity were required under the conditions of our experiments

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