Key pointsr This paper provides a comprehensive electrophysiological characterization of the external [K + ] dependence and inward rectifying properties of Kir channels in fast skeletal muscle fibres of adult mice.r Two isoforms of inward rectifier K channels (IKir2.1 and IKir2.2) are expressed in both the surface and the transverse tubular system (TTS) membranes of these fibres.r Optical measurements demonstrate that Kir currents (IKir) affect the membrane potential changes in the TTS membranes, and result in a reduction in luminal [r A model of the muscle fibre assuming that functional Kir channels are equally distributed between the surface and TTS membranes accounts for both the electrophysiological and the optical data.r Model simulations demonstrate that the more than 70% of IKir arises from the TTS membranes.increases in the lumen of the TTS resulting from the activation of K delayed rectifier channels (Kv) lead to drastic enhancements of IKir, and to right-shifts in their reversal potential. These changes are predicted by the model.
AbstractInward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K + ], and could be blocked by Ba 2+ or Rb + . In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba 2+ (or Rb + ) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K + ] (96 and 24 mM), were closely predicted by assuming Kir permeability (PKir) values of ß5.5 × 10 −6 cm s −1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K + depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of mos...