Voltage-sensor relaxation in Hv1 proton channels


Carlos A. Villalba-Galea: 0000-0002-6489-4651

Document Type

Conference Presentation

Conference Title/Conference Publication

Biophysical Journal


Biophysical Society 55th Annual Meeting


Baltimore, MD

Conference Dates

March 5-9, 2011

Date of Presentation







3, Supplement 1



First Page


Last Page



Hv1 is a voltage-gated and proton-selective channel composed of four helical transmembrane segments (S1-S4) that adopt a voltage-sensor (VS) domain fold that is common to voltage-dependent ion channels and voltage-sensitive phosphatases (VSPs). Unlike other voltage-gated channels, the Hv1 VS also functions as a sensor for the transmembrane pH gradient and contains a water-wire for H+ conduction. However, despite exhibiting biophysical properties that are specific to its proton channel function, the Hv1 VS appears to share significant structural and functional homology with other VS domains. VS relaxation is manifested by a negative shift in the voltage dependence of sensing charge (Q) movement in response to prolonged depolarization. Previous studies on ciVSP led to the hypothesis that depolarization-induced movement of S4 leads to a rapid distortion of the VS structure. A compensatory voltage-independent conformational transition termed relaxation allows the VS to adopt a more thermodynamically stable state, and is revealed by a negative shift in the Q-V relation. We postulated that because relaxation is likely to represent an intrinsic feature of VS domain function, Hv1 VS would also enter a relaxed state after sustained depolarization. In order to test this hypothesis, we elicited Hv1 opening by applying voltage steps to positive potentials for varying durations and then measured the voltage dependence of channel closure (V0.5). As predicted, depolarizing pre-pulses caused V0.5 to shift toward negative potentials. The magnitude of the shift in V0.5 was observed to depend on the duration of the prepulse over the range of 0.1-5.0 s. These observations demonstrate that Hv1 manifests VS relaxation and suggest that relaxation occurs concomitantly with proton channel opening.