Fig. 4. Effects of caffeine in partially depolarized malignant hyperthermia–nonsusceptible (MHN) muscle fiber with a physiologic myoplasmic free calcium concentration ([Ca2+]i). Simultaneous recording, using a double-barreled microelectrodes, of Vm and [Ca2+]iin a MHN in swine physiologic solution (first panel ), 10 mm K+solution (second panel ) after[Ca2+]ihas returned to control levels (third panel ) and after the application of caffeine 2 mm (fourth panel ). In control, Vm was −82 mV and [Ca2+]iwas 125 nm. The incubation of a MHN muscle fiber in K+10 mm solution induced a partial depolarization (Vm =−71 mV) that was associated with a transient elevation of [Ca2+]ito 296 nm, which returned to 130 nm after 8 min. Exposure of this still partially depolarized muscle fiber to 2 mm caffeine after [Ca2+]ireturned to control levels caused an elevation of [Ca2+]ito 320 nm, which was the same as was seen in control polarized cells. All of the measurements for Vm and [Ca2+]iwere conducted in same muscle fiber. (Left and right ) Calibration bars for the Ca2+-selective microelectrode and the resting membrane potential, respectively, are shown.