Dilation of ion selectivity filters in cation channels

Dilated selectivity filters observed in inactivated voltage-activated K+ channel structures reveal that larger pores can result in reduced ion permeation.Functional experiments measuring changes in reversal potential in response to sustained activation of P2X and transient receptor potential (TRP) channels may be due to ion accumulation and depletion rather than pore dilation causing changes in ion selectivity.Relatively large cations can permeate through the pores of P2X and TRP channels, but whether pore dilation is required remains poorly understood.Pore dilation in TRP channels was recently proposed to result from changes in the oligomeric state of the channel. Ion channels establish the voltage gradient across cellular membranes by providing aqueous pathways for ions to selectively diffuse down their concentration gradients. The selectivity of any given channel for its favored ions has conventionally been viewed as a stable property, and in many cation channels, it is determined by an ion-selectivity filter within the external end of the ion-permeation pathway. In several instances, including voltage-activated K+ (Kv) channels, ATP-activated P2X receptor channels, and transient receptor potential (TRP) channels, the ion-permeation pathways have been proposed to dilate in response to persistent activation, dynamically altering ion permeation. Here, we discuss evidence for dynamic ion selectivity, examples where ion selectivity filters exhibit structural plasticity, and opportunities to fill gaps in our current understanding. Ion channels establish the voltage gradient across cellular membranes by providing aqueous pathways for ions to selectively diffuse down their concentration gradients. The selectivity of any given channel for its favored ions has conventionally been viewed as a stable property, and in many cation channels, it is determined by an ion-selectivity filter within the external end of the ion-permeation pathway. In several instances, including voltage-activated K+ (Kv) channels, ATP-activated P2X receptor channels, and transient receptor potential (TRP) channels, the ion-permeation pathways have been proposed to dilate in response to persistent activation, dynamically altering ion permeation. Here, we discuss evidence for dynamic ion selectivity, examples where ion selectivity filters exhibit structural plasticity, and opportunities to fill gaps in our current understanding.