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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 excitationcontraction (EC) coupling and the charge movement component q
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
and qh moved by
90% and
55%, respectively, whereas 1-alkanols completely abolished them. Ryanodine and RR shifted the transition voltages of q
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
; 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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