Hysteretic Behavior in Voltage-Gated Channels

Abstract

An ever-growing body of evidence has shown that voltage-gated ion channels are likely molecular systems that display hysteresis in their activity. This phenomenon manifests in the form of dynamic changes in both their voltage dependence of activity and their deactivation kinetics. The goal of this review is to provide a clear definition of hysteresis in terms of the behavior of voltage-gated channels. This review will discuss the basic behavior of voltage-gated channel activity and how they make these proteins into systems displaying hysteresis. It will also provide a perspective on putative mechanisms underlying hysteresis and explain its potential physiological relevance. It is uncertain whether all channels display hysteresis in their behavior. However, the suggested notion that ion channels are hysteretic systems directly collides with the well-accepted notion that ion channel activity is stochastic. This is because hysteretic systems are regarded to have “memory” of previous events while stochastic processes are regarded as “memoryless.” This review will address this apparent contradiction, providing arguments for the existence of processes that can be simultaneously hysteretic and stochastic.

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K+ Current

“…The voltage hysteresis of ionic currents (i.e., a lag in the current magnitude as the linear voltage command is changed in the opposite direction) has been demonstrated with a notable impact on the electrical signal events of different excitable cells [ 25 , 34 , 35 , 36 , 37 ]. In other words, hysteretic behavior is thought to dynamically adjust the voltage sensitivity and kinetics to optimize channel function for matching its physiological role.…”

“…In accordance with previous observations [ 25 ], the voltage-dependent hysteresis of I K(M) in response to the long isosceles-triangular ramp pulse was demonstrated in GH 3 cells. The strength of such hysteretic perturbations was recently described to serve a role in tuning the activity of K M channels to respond as they are needed [ 37 ]. We also further determined the possible adjustments of KYNA on such non-equilibrium property of I K(M) present in GH 3 cells.…”

“…The relationship between the membrane potentials and the I K(M) conductance obtained with and without the application of KYNA (30 μM) or KYNA-A4 (10 μM) was appropriately fitted with a modified Boltzmann function (or the Fermi-Dirac distribution) of the following form [ 37 ]: where G max denotes the maximal conductance of I K(M) , V 1/2 is the voltage at which half-maximal activation of the current is achieved, q is the apparent gating charge, F is Faraday’s constant, R is the universal gas constant, and T is the absolute temperature.…”

“…The concentration-response data for stimulation of I K(M) were thereafter least-squares fitted to the modified Hill equation (i.e., multi-parameter logistic equation). That is, The relationship between the membrane potentials and the I K(M) conductance obtained with and without the application of KYNA (30 µM) or KYNA-A4 (10 µM) was appropriately fitted with a modified Boltzmann function (or the Fermi-Dirac distribution) of the following form [37]:…”

Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker

“…bid=60015, accessed on 4 April 2012, Hsinchu, Taiwan) [32], while the MMQ cell line (ATCC ® CRL-10609, https://www.atcc.org/products/all/CRL-10609.aspx, accessed on 18 April 2019), another established pituitary cell line originally derived from Rattus norvegicus pituitary prolactinoma, was from the American Type Cell Collection (Manassas, VA, USA) through Genechain (Kaohsiung, Taiwan). GH 3 cells were maintained in Ham's F-12 culture medium supplemented with 2.5% fetal bovine serum (v/v), 15% horse serum (v/v), and 2 mM L-glutamine [31], and MMQ cells were cultured in F12 medium supplemented with 10% fetal bovine serum (v/v) and 1.176 g/L NaHCO 3 in a humidified incubator at 30 • C with 5% CO 2 [33]. The cells were grown as a monolayer culture in a humidified environment of 5% CO 2 /95% air at 37 • C. The electrophysiological recordings were commonly made five or six days after the cells had been cultured to 60-80% confluence.…”