Premium
A Role for the Excess Ryanodine Receptors in Excitation‐Contraction Coupling
Author(s) -
Pitake Saumitra,
Ochs Raymond S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1047.5
Subject(s) - ryanodine receptor , endoplasmic reticulum , chemistry , biophysics , activator (genetics) , cytosol , caffeine , contraction (grammar) , receptor , depolarization , calcium , ryr1 , medicine , endocrinology , biochemistry , biology , organic chemistry , enzyme
A close interaction between the plasma membrane bound DHPR (dihydropyridine receptor, the sensor of electrical changes in the membrane) and the endoplasmic reticulum bound RyR (ryanodine receptor, the Ca 2+ release channel to the cytosol) is central to excitation‐contraction coupled Ca 2+ release (ECC) by skeletal muscle. We hypothesized that the 2:1 ratio of RyR:DHPR may reflect relative movement of DHPR and RyR accompanied by bursts of Ca 2+ release. We tested the hypothesis by measuring the sensitivity of the RyR and DHPR to modulators of these proteins. The response of RyR (measured as Ca 2+ appearance in the cytosol) to its namesake modulator ryanodine (Ry) was shifted to lower concentrations of Ry when cells were subjected to field depolarization. In a similar way, Ca 2+ release in response to the DHPR activator BayK was also shifted to lower concentrations of BayK when cells were depolarized. However, sensitivity of Ca 2+ release to these agents was not altered when either the direct RyR activator CMC (a caffeine‐like agent) or increased medium Ca 2+ was applied. While some studies have suggested that RyR may not be essential in ECC, this was based on very high concentrations of Ry (above 100 μM). Yet, we found that cells incubated with Ry at 10 μM completely blocked ECC. Ry at concentrations greater than 50 μM compromised cell viability. Our findings support an interaction model of DHPR and RyR in ECC, a role for the excess number of RyR over DHPR, and indicate Ca 2+ release for ECC is exclusively through the RyR.