Activation of the archaeal ion channel MthK is exquisitely regulated by temperature.

Yihao Jiang,Vinay Idikuda,Baron Chanda,Sandipan Chowdhury

doi:10.7554/elife.59055

Yihao Jiang, Vinay Idikuda + Show 2 more

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https://doi.org/10.7554/elife.59055

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Abstract

Physiological response to thermal stimuli in mammals is mediated by a structurally diverse class of ion channels, many of which exhibit polymodal behavior. To probe the diversity of biophysical mechanisms of temperature-sensitivity, we characterized the temperature-dependent activation of MthK, a two transmembrane calcium-activated potassium channel from thermophilic archaebacteria. Our functional complementation studies show that these channels are more efficient at rescuing K+ transport at 37°C than at 24°C. Electrophysiological activity of the purified MthK is extremely sensitive (Q10 >100) to heating particularly at low-calcium concentrations whereas channels lacking the calcium-sensing RCK domain are practically insensitive. By analyzing single-channel activities at limiting calcium concentrations, we find that temperature alters the coupling between the cytoplasmic RCK domains and the pore domain. These findings reveal a hitherto unexplored mechanism of temperature-dependent regulation of ion channel gating and shed light on ancient origins of temperature-sensitivity.

Highlights

Ion channels act both as gatekeepers and signal transducers responding to a variety of environmental cues including both physical and chemical stimuli
To probe the temperature sensitivity of MthK in bacteria, we utilized a complementation assay based on E. coli potassium-uptake deficient LB2003 strain (Stumpe and Bakker, 1997)
Previous studies have shown that increased rescue of LB2003 strain can be directly correlated with a higher open probability of the expressed potassium channels (Cuello et al, 2010b)

Summary

Introduction

Ion channels act both as gatekeepers and signal transducers responding to a variety of environmental cues including both physical and chemical stimuli. As far as we know, these channels lack a common structural motif for sensing temperature, unlike their ligand activated counterparts This lack of conserved structural module is not surprising given that sensors of physical stimuli are not constrained by a specific domain in contrast to chemical sensors (Kuriyan et al, 2012; Goldschen-Ohm and Chanda, 2017). From a mechanistic standpoint, these physical force-sensing ion channels are referred to as Type III channels to distinguish them from ligand-activated ion channels which typically harbor conserved structural motifs (Goldschen-Ohm and Chanda, 2017)

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