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J Physiol Volume 555, Number 1, 137-152, February 15, 2004 DOI: 10.1113/jphysiol.2003.051730
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L-type Ca2+ channel and ryanodine receptor cross-talk in frog skeletal muscle

Roberta Squecco, Chiara Bencini, Claudia Piperio and Fabio Francini

Department of Physiological Sciences, University of Florence, Viale GB Morgagni 63, I-50134 Firenze, Italy

The dihydropyridine receptors (DHPRs)/L-type Ca2+ channels of skeletal muscle are coupled with ryanodine receptors/Ca2+ 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{gamma} has been implicated as the signal linking DHPR voltage sensing to Ca2+ release from the coupled RyR. Recently, a new charge component, qh, has been described and related to L-type Ca2+ 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 qh is also involved in the reciprocal interaction or cross-talk between DHPR/L-type Ca2+ channel and RyR/CRC. To this end we interfered with DHPR/L-type Ca2+ 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 Ca2+ current (ICa) 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{gamma} and qh moved by ~90% and ~55%, respectively, whereas 1-alkanols completely abolished them. Ryanodine and RR shifted the transition voltages of q{gamma} and qh and of the maximal conductance of ICa by ~4-9 mV towards positive potentials. All these interventions spared qß. These results support the hypothesis that only q{gamma}; and qh arise from the movement of charged particles within the DHPR/L-type Ca2+ channel and that these charge components together with ICa are affected by a retrograde signal from RyR/CRC.

(Received 16 September 2003; accepted after revision 5 December 2003; first published online 5 December 2003)
Corresponding author F. Francini: Department of Physiological Sciences, University of Florence, Viale G.B. Morgagni, 63, 50134 Florence, Italy.  Email: fabio.francini{at}unifi.it







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