Figure 6.
(A)(a) Double pulse protocol from a hyperpolarized prepulse potential V0 to activating voltage V1 followed by further depolarization to fixed depolarized voltage V2, respectively assessing (b) Na+ current activation and subsequent inactivation produced by the voltage step to V1. (B) 2–10 mM caffeine increases integrated background aequorin Ca2+ signal (upper trace) and twitch force (lower trace) in rat fast twitch muscle at 25°C over timecourses dependent upon caffeine concentration. Arrows denote periods of caffeine exposure. (C) Families of loose-patch clamp membrane currents in response to the double pulse protocol before (a, b) and at successive intervals ((i)-(iv)) following introduction (c, d) of caffeine (0.5 mM) before (a, c) and following (b, d) addition of dantrolene (10 µM). Currents expressed as current densities (pA/µm2) through 28–32 µm pipette diameters.((A) from Figure 2 by permission (Fryer & Neering [47]); (B) from Figure 3 by permission (Sarbjit-Singh et al. [48]).
Na+ current down-regulation in native murine skeletal muscle fibres by altered Ca2+ homeostasis following caffeine induced ryanodine receptor (RyR) activation, abrogated by dantrolene mediated RyR antagonism.

(A)(a) Double pulse protocol from a hyperpolarized prepulse potential V0 to activating voltage V1 followed by further depolarization to fixed depolarized voltage V2, respectively assessing (b) Na+ current activation and subsequent inactivation produced by the voltage step to V1. (B) 2–10 mM caffeine increases integrated background aequorin Ca2+ signal (upper trace) and twitch force (lower trace) in rat fast twitch muscle at 25°C over timecourses dependent upon caffeine concentration. Arrows denote periods of caffeine exposure. (C) Families of loose-patch clamp membrane currents in response to the double pulse protocol before (a, b) and at successive intervals ((i)-(iv)) following introduction (c, d) of caffeine (0.5 mM) before (a, c) and following (b, d) addition of dantrolene (10 µM). Currents expressed as current densities (pA/µm2) through 28–32 µm pipette diameters.((A) from Figure 2 by permission (Fryer & Neering [47]); (B) from Figure 3 by permission (Sarbjit-Singh et al. [48]).

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