Inward rectifier potassium currents in mammalian skeletal muscle fibres

Abstract

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...

A skeletal muscle L-type Ca2+ channel with a mutation in the selectivity filter (CaV1.1 E1014K) conducts K+

“…As described above, endogenous delayed rectifier K + channels provide an avenue for K + efflux into the lumen during HFS or prolonged depolarization in wild-type muscle ( Fig. 6A; 34,35,43). The introduction of a substantial K + conductance via every single Ca V 1.1 channel in Ca V 1.1 E1014K muscle would accelerate the elevation of the local membrane potential, resulting in action potential and EC coupling failure leading to more rapid declines in force (Fig.…”

“…During LFS, these clearance mechanisms are sufficient to maintain the K + gradient (31). However, transport by the pump and inward rectifier channels cannot keep pace with the K + efflux via delayed rectifier channels during prolonged depolarization or HFS protocols similar to those employed by Lee and colleagues (15,30,[33][34][35][36][37][38][39]. Even with the assistance of Cl -flux via ClC-1 channels in stabilizing the resting potential, the result is net K + accumulation sufficient to elevate the local membrane potential to a point at which Na + channels inactivate (30, 40).…”

“…During the repolarization phase of the skeletal muscle action potential, K + exits the myoplasm via delayed rectifier K + channels to restricted extracellular compartments before being returned actively to the fiber by the Na + /K + -ATPase (31) or passively via inward rectifier K + channels when the membrane potential becomes more negative than E K (32)(33)(34)(35). During LFS, these clearance mechanisms are sufficient to maintain the K + gradient (31).…”

“…[33][34][35]. Specifically, a higher conductance and a more profound depolarizing shift in the reversal potential for the inward rectifier current in Ca V 1.1 E1014K fibers relative to wild-type and Ca V 1.1 N617D fibers would be evident if elevated extracellular K + levels underlie the accelerated decay of Ca 2+ transient amplitudes during HFS.…”

Bitter Taste Receptors as Regulators of Abdominal Muscles Contraction

“…Another set of experiments targeted Kir channels. It is generally accepted that Kir2.1 and Kir2.2 channels are the prevalent forms of Kir channels in skeletal muscles (DiFranco et al 2015). They are present either on the surface (about 30 %) or in T-tubules (about 70 %) of fibres (DiFranco et al 2015).…”