Induction of pseudo‐periodic oscillation in voltage‐gated sodium channel properties is dependent on the duration of prolonged depolarization

Majumdar, Sriparna; Foster, Grant; Sikdar, Sujit Kumar

doi:10.1111/j.1460-9568.2004.03466.x

Cited by 6 publications

(2 citation statements)

References 53 publications

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“…Resting potential-dependent regulation of sodium channel gating may also play a role in diseases of excitability in brain and heart. The phenomenon has been reported in the Nav1.5 isoform (expressed in cardiac muscle) (Kimitsuki et al, 1990) and may occur in the Nav1.2 isoform (expressed in neurons) (Majumdar et al, 2004). Changes in the voltage dependence of gating of the Nav1.5 sodium channel could play an important role in preventing arrhythmias during cardiac depolarization due to ischemia.…”

Section: Functional Implicationsmentioning

confidence: 93%

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Filatov

Pinter

Rich

2005

The Journal of General Physiology

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Normal muscle has a resting potential of −85 mV, but in a number of situations there is depolarization of the resting potential that alters excitability. To better understand the effect of resting potential on muscle excitability we attempted to accurately simulate excitability at both normal and depolarized resting potentials. To accurately simulate excitability we found that it was necessary to include a resting potential–dependent shift in the voltage dependence of sodium channel activation and fast inactivation. We recorded sodium currents from muscle fibers in vivo and found that prolonged changes in holding potential cause shifts in the voltage dependence of both activation and fast inactivation of sodium currents. We also found that altering the amplitude of the prepulse or test pulse produced differences in the voltage dependence of activation and inactivation respectively. Since only the Nav1.4 sodium channel isoform is present in significant quantity in adult skeletal muscle, this suggests that either there are multiple states of Nav1.4 that differ in their voltage dependence of gating or there is a distribution in the voltage dependence of gating of Nav1.4. Taken together, our data suggest that changes in resting potential toward more positive potentials favor states of Nav1.4 with depolarized voltage dependence of gating and thus shift voltage dependence of the sodium current. We propose that resting potential–induced shifts in the voltage dependence of sodium channel gating are essential to properly regulate muscle excitability in vivo.

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Section: Functional Implicationsmentioning

confidence: 93%

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Filatov

Pinter

Rich

2005

The Journal of General Physiology

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“…The pulse train protocol is a popular and a very powerful nonequilibrium spectroscopic tool to study the channel gating process, inactivation procedure and recovery from inactivation. [42][43][44][45] Here we want to investigate the path of inactivation in presence of consecutive test pulses and base pulses. The pulse train is applied in the following manner.…”

Section: Pulse Train Protocolmentioning

confidence: 99%

Dynamical characterization of inactivation path in voltage-gated Na⁺ion channel by non-equilibrium response spectroscopy

Pal

Gangopadhyay

2016

Channels

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Inactivation path of voltage gated sodium channel has been studied here under various voltage protocols as it is the main governing factor for the periodic occurrence and shape of the action potential. These voltage protocols actually serve as non-equilibrium response spectroscopic tools to study the ion channel in non-equilibrium environment. In contrast to a lot of effort in finding the crystal structure based molecular mechanism of closed-state(CSI) and open-state inactivation(OSI); here our approach is to understand the dynamical characterization of inactivation. The kinetic flux as well as energetic contribution of the closed and open- state inactivation path is compared here for voltage protocols, namely constant, pulsed and oscillating. The non-equilibrium thermodynamic quantities used in response to these voltage protocols serve as improved characterization tools for theoretical understanding which not only agrees with the previously known kinetic measurements but also predict the energetically optimum processes to sustain the auto-regulatory mechanism of action potential and the consequent inactivation steps needed. The time dependent voltage pattern governs the population of the conformational states which when couple with characteristic rate parameters, the CSI and OSI selectivity arise dynamically to control the inactivation path. Using constant, pulsed and continuous oscillating voltage protocols we have shown that during depolarization the OSI path is more favored path of inactivation however, in the hyper-polarized situation the CSI is favored. It is also shown that the re-factorisation of inactivated sodium channel to resting state occurs via CSI path. Here we have shown how the subtle energetic and entropic cost due to the change in the depolarization magnitude determines the optimum path of inactivation. It is shown that an efficient CSI and OSI dynamical profile in principle can characterize the open-state drug blocking phenomena.

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Fast Pseudo-Periodic Oscillation in the Rat Brain Voltage-gated Sodium Channel α Subunit

Majumdar

Sikdar

2005

J Membrane Biol

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In the work reported here, we have investigated the changes in the activation and fast inactivation properties of the rat brain voltage-gated sodium channel (rNa(v) 1.2a) alpha subunit, expressed heterologously in the Chinese Hamster Ovary (CHO) cells, by short depolarizing prepulses (10-1000 ms). The time constant of recovery from fast inactivation (tau(fast)) and steady-state parameters for activation and inactivation varied in a pseudo-oscillatory fashion with the duration and amplitude of a sustained prepulse. A consistent oscillation was observed in most of the steady-state and non-inactivating current parameters with a time period close to 225 ms, although a faster oscillation of time period 125 ms was observed in the tau(fast). The studies on the non-inactivating current and steady-state activation indicate that the phase of oscillation varies from cell to cell. Co-expression of the beta1 subunit with the alpha subunit channel suppressed the oscillation in the charge movement per single channel and free energy of steady-state inactivation, although the oscillation in the half steady-state inactivation potential remained unaltered. Incidentally, the frequencies of oscillation in the sodium channel parameters (4-8 Hz) correspond to the theta component of network oscillation. This fast pseudo-oscillatory mechanism, together with the slow pseudo-oscillatory mechanism found in these channels earlier, may contribute to the oscillations in the firing properties observed in various neuronal subtypes and many pathological conditions.

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Induction of pseudo‐periodic oscillation in voltage‐gated sodium channel properties is dependent on the duration of prolonged depolarization

Cited by 6 publications

References 53 publications

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Dynamical characterization of inactivation path in voltage-gated Na⁺ion channel by non-equilibrium response spectroscopy

Fast Pseudo-Periodic Oscillation in the Rat Brain Voltage-gated Sodium Channel α Subunit

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Induction of pseudo‐periodic oscillation in voltage‐gated sodium channel properties is dependent on the duration of prolonged depolarization

Cited by 6 publications

References 53 publications

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo

Dynamical characterization of inactivation path in voltage-gated Na+ion channel by non-equilibrium response spectroscopy

Fast Pseudo-Periodic Oscillation in the Rat Brain Voltage-gated Sodium Channel α Subunit

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Dynamical characterization of inactivation path in voltage-gated Na⁺ion channel by non-equilibrium response spectroscopy