L-type Ca2+ channel and ryanodine receptor cross-talk in frog skeletal muscle.
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 approximately 90% and approximately 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 approximately 4-9 mV towards positive potentials. All these interventions spared q beta. 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.
Squecco
Roberta
R
Department of Physiological Sciences, University of Florence, Viale G.B. Morgagni 63, I-50134 Florence, Italy.
Bencini
Chiara
C
Piperio
Claudia
C
Francini
Fabio
F
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011893:Rana esculenta; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D009543:Nifedipine