Troponin I converts the skeletal muscle ryanodine receptor into a rectifying calcium release channel.
The goal of our present studies has been to find novel ryanodine receptor (RyR1) interacting polypeptides that modulate the channel activity from the luminal side of RyR1. Using K(+) as charge carrier for recording of single channel events here we demonstrate a very unexpected observation that troponin I substantially alters RyR's gating behavior, and that RyR1 in association with troponin I becomes a rectifying Ca(2+) release channel. Troponin I rapidly locks the RyR1 in a non-conducting state only at a negative holding potential, and only when applied to the luminal side; switching to a positive holding potential results in the channel returning to its original activity, immediately. A hypothesis is proposed to account for how an intraluminally located, positively charged molecule might function as a RyR1 regulator under physiological conditions.
Varsányi
Magdolna
M
Institut für Physiologische Chemie, Ruhr Universität, D-44780, Bochum, Germany. magdolna.varsanyi@ruhr-uni-bochum.de
Sárközi
Sándor
S
Szegedi
Csaba
C
Herzog
Anke
A
Jóna
István
I
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000737:chemistry*; D011188:Potassium / Q000378:metabolism; D021122:Protein Subunits; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000737:chemistry; D019210:Troponin I / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D015220:Calcium Channels; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D021122:Protein Subunits; D019837:Ryanodine Receptor Calcium Release Channel; D019210:Troponin I; D011188:Potassium