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

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Abstract
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 qγ 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 qγ and qh moved by ∼90% and ∼55%, respectively, whereas 1-alkanols completely abolished them. Ryanodine and RR shifted the transition voltages of qγ and qh and of the maximal conductance of ICa by ∼4−9 mV towards positive potentials. All these interventions spared qβ. These results support the hypothesis that only qγ; 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.