L‐type Ca 2+ 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 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.