Hysteresis in voltage-gated channels

Abstract

Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.

Inverse Modulation of Neuronal Kv12.1 and Kv11.1 Channels by 4-Aminopyridine and NS1643

“…To minimize time intervals at hyperpolarized potentials that may counteract mode shift (c.f. Villalba-Galea, 2017 ), we at start recorded tail currents at correspondingly depolarized potentials ( Figures 1G – I ). In these experiments, amplitudes of K v 12.1-mediated outward currents were similar irrespective of conditioning potentials.…”

“…We found that mode shift of human K v 12.1 was readily induced by depolarized holding potentials between -60 and 0 mV and that it manifested by slowed channel deactivation and a striking shift of voltage dependence to hyperpolarized potentials. Deceleration of deactivation is generally considered a biophysical hallmark of mode shift, as channels undergo additional (time-consuming) transitions from this “relaxed” (metastable) open state into deactivation ( Bezanilla et al, 1982 ; Villalba-Galea et al, 2008 ; Corbin-Leftwich et al, 2016 ; Villalba-Galea, 2017 ). Similar to K v 11.1 ( Tan et al, 2012 ) and zebrafish K v 12.1 ( Dai and Zagotta, 2017 ), mode shift of human K v 12.1 channels manifested by a striking -60 mV shift of voltage dependence.…”

The voltage sensor of excitation–contraction coupling in mammals: Inactivation and interaction with Ca2+

“…Based largely on the equality of Q max in both conditions of polarization found for sensors of Na V channels of the squid giant axon, Bezanilla et al (1982) proposed that the currents correspond to transitions between separate pairs of conformations of the same voltage sensor (later identified with charge 1 and charge 2 modes in skeletal muscle). A shift of Q ( V ) toward negative voltages upon sustained depolarization turned out to be shared by all known four-helix VSMs (reviewed by Villalba-Galea, 2012 , 2016 ).…”

“…The description of VSM states by Scheme 1 is therefore approximately valid for every four-helix VSM in which charge movements have been measured. VSM relaxation was reviewed recently within the wider set of hysteresis phenomena ( Villalba-Galea, 2016 ).…”

Site and Mechanism of Action of Resin Acids on Voltage-Gated Ion Channels

“…The inactivation gate is removed, and the pore closes when the voltage sensor no longer pulls on the S4-S5 linker. The rate of the deactivation can vary depending on the preceding voltage, which cause a so called 'mode-shift', that is common for many channels (Elinder et al, 2006;Labro et al, 2012;Villalba-Galea, 2016). …”