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L-type Ca2+ channel and ryanodine receptor cross-talk in frog skeletal muscle

The dihydropyridine receptors (DHPRs) /L -type Ca 2+ channels of skeletal muscle are coupled with ryanodine receptors/Ca 2+ release channels (RyRs/CRCs) located in the sarcoplasmic reticulum (SR). The DHPR is the voltage sensor for excitation–contraction (EC) coupling and the charge movement compo...

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Bibliographic Details
Published in:The Journal of physiology 2004-02, Vol.555 (1), p.137-152
Main Authors: Squecco, Roberta, Bencini, Chiara, Piperio, Claudia, Francini, Fabio
Format: Article
Language:English
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Summary:The dihydropyridine receptors (DHPRs) /L -type Ca 2+ channels of skeletal muscle are coupled with ryanodine receptors/Ca 2+ release channels (RyRs/CRCs) located in the sarcoplasmic reticulum (SR). The DHPR is the voltage sensor for excitation–contraction (EC) coupling and the charge movement component q γ has been implicated as the signal linking DHPR voltage sensing to Ca 2+ release from the coupled RyR. Recently, a new charge component, q h , has been described and related to L- type Ca 2+ channel gating. Evidence has also been provided that the coupled RyR/CRC can modulate DHPR functions via a retrograde signal. Our aim was to investigate whether the newly described q h is also involved in the reciprocal interaction or cross-talk between DHPR/ L- type Ca 2+ channel and RyR/CRC. To this end we interfered with DHPR/ L- type Ca 2+ channel function using nifedipine and 1-alkanols (heptanol and octanol), and with RyR/CRC function using ryanodine and ruthenium red (RR). Intramembrane charge movement (ICM) and L- type Ca 2+ current ( I Ca ) were measured in single cut fibres of the frog using the double-Vaseline-gap technique. Our records showed that nifedipine reduced the amount of q γ and q h moved by ∼90% and ∼55%, respectively, whereas 1-alkanols completely abolished them. Ryanodine and RR shifted the transition voltages of q γ and q h and of the maximal conductance of I Ca by ∼4−9 mV towards positive potentials. All these interventions spared q β . These results support the hypothesis that only q γ ; and q h arise from the movement of charged particles within the DHPR/ L- type Ca 2+ channel and that these charge components together with I Ca are affected by a retrograde signal from RyR/CRC.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2003.051730