scholarly journals Decision letter: Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing

2020 ◽  
Author(s):  
Arpad Mike ◽  
Bruce P Bean
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Neuronal Firing ◽  
Leaky Integrator

scholarly journals Author response: Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing

2020 ◽  
Author(s):  
Marco A Navarro ◽  
Autoosa Salari ◽  
Jenna L Lin ◽  
Luke M Cowan ◽  
Nicholas J Penington ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Neuronal Firing ◽  
Author Response ◽  
Leaky Integrator

scholarly journals Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marco A Navarro ◽  
Autoosa Salari ◽  
Jenna L Lin ◽  
Luke M Cowan ◽  
Nicholas J Penington ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Critical Role ◽  
Low Frequency ◽  
Kinetic Mechanism ◽  
Excitatory Input ◽  
Neuronal Firing ◽  
Na Current ◽  
Brain Functions ◽  
Leaky Integrator

Voltage-gated sodium channels play a critical role in cellular excitability, amplifying small membrane depolarizations into action potentials. Interactions with auxiliary subunits and other factors modify the intrinsic kinetic mechanism to result in new molecular and cellular functionality. We show here that sodium channels can implement a molecular leaky integrator, where the input signal is the membrane potential and the output is the occupancy of a long-term inactivated state. Through this mechanism, sodium channels effectively measure the frequency of action potentials and convert it into Na+ current availability. In turn, the Na+ current can control neuronal firing frequency in a negative feedback loop. Consequently, neurons become less sensitive to changes in excitatory input and maintain a lower firing rate. We present these ideas in the context of rat serotonergic raphe neurons, which fire spontaneously at low frequency and provide critical neuromodulation to many autonomous and cognitive brain functions.

scholarly journals Sodium Channels Implement a Molecular Leaky Integrator to Sense Spiking Frequency and Regulate Neuronal Firing

2019 ◽  
Vol 116 (3) ◽  
pp. 388a
Author(s):  
Marco A. Navarro ◽  
Jenna Lin ◽  
Autoosa Salari ◽  
Mirela Milescu ◽  
Lorin S. Milescu
Keyword(s):  
Sodium Channels ◽  
Neuronal Firing ◽  
Leaky Integrator

scholarly journals A sensory integration account for time perception

2020 ◽  
Author(s):  
Alessandro Toso ◽  
Arash Fassihi ◽  
Luciano Paz ◽  
Francesca Pulecchi ◽  
Mathew E. Diamond
Keyword(s):  
Time Perception ◽  
Time Constant ◽  
Sensory Integration ◽  
Neuronal Firing ◽  
Elapsed Time ◽  
Leaky Integrator ◽  
Long Time ◽  
Integrator Model ◽  
Short Time ◽  
Sense Of Touch

ABSTRACTThe connection between stimulus perception and time perception remains unknown. The present study combines human and rat psychophysics with sensory cortical neuronal firing to construct a computational model for the percept of elapsed time embedded within sense of touch. When subjects judged the duration of a vibration applied to the fingertip (human) or whiskers (rat), increasing stimulus mean speed led to increasing perceived duration. Symmetrically, increasing vibration duration led to increasing perceived intensity. We modeled spike trains from vibrissal somatosensory cortex as input to dual leaky integrators – an intensity integrator with short time constant and a duration integrator with long time constant – generating neurometric functions that replicated the actual psychophysical functions of rats. Returning to human psychophysics, we then confirmed specific predictions of the dual leaky integrator model. This study offers a framework, based on sensory coding and subsequent accumulation of sensory drive, to account for how a feeling of the passage of time accompanies the tactile sensory experience.

Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons

2001 ◽  
Vol 86 (2) ◽  
pp. 629-640 ◽  
Author(s):  
Muthukrishnan Renganathan ◽  
Theodore R. Cummins ◽  
Stephen G. Waxman
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Current Threshold

C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Nav1.8 (+/+) and (−/−) small DRG neurons maintained for 2–8 h in vitro to examine the role of sodium channel Nav1.8 (α-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Nav1.8 (+/+) and (−/−) DRG neurons, there were significant differences in action potential electrogenesis. Most Nav1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Nav1.8 (−/−) neurons produce smaller graded responses. The peak of the response was significantly reduced in Nav1.8 (−/−) neurons [31.5 ± 2.2 (SE) mV] compared with Nav1.8 (+/+) neurons (55.0 ± 4.3 mV). The maximum rise slope was 84.7 ± 11.2 mV/ms in Nav1.8 (+/+) neurons, significantly faster than in Nav1.8 (−/−) neurons where it was 47.2 ± 1.3 mV/ms. Calculations based on the action potential overshoot in Nav1.8 (+/+) and (−/−) neurons, following blockade of Ca2+ currents, indicate that Nav1.8 contributes a substantial fraction (80–90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na+ channels can produce all-or-none action potentials in some Nav1.8 (−/−) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Nav1.8 (−/−) neurons is more sensitive to membrane depolarization than in Nav1.8 (+/+) neurons, and, in the absence of Nav1.8, is attenuated with even modest depolarization. These observations indicate that Nav1.8 contributes substantially to action potential electrogenesis in C-type DRG neurons.

Excitable Membrane Properties of Neurons

2020 ◽  
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Cell Biology ◽  
Neuronal Firing ◽  
Membrane Properties ◽  
Potassium Ions ◽  
Single Action ◽  
Sodium Calcium ◽  
Different Types ◽  
Order Of Magnitude

The intrinsic electrical properties of neurons are extremely varied. For example, the width of action potentials in different neurons varies by more than an order of magnitude. In response to prolonged stimulation, some neurons generate repeated action potential hundreds of times a second, while others fire only a single action potential or adapt very rapidly. These differences result from the expression of different types of ion channels in the plasma membrane. The dominant channels that shape neuronal firing patterns are those that are selective for sodium, calcium, and potassium ions. This chapter provides a brief overview of the biophysical properties of each of these classes of channel, their role in shaping the electrical personality of a neuron, and how interactions of these channels with cytoplasmic factors shape the overall cell biology of a neuron.

Control of neuronal excitability by phosphorylation and dephosphorylation of sodium channels

2006 ◽  
Vol 34 (6) ◽  
pp. 1299-1302 ◽  
Author(s):  
T. Scheuer ◽  
W.A. Catterall
Keyword(s):  
Protein Kinases ◽  
Sodium Channels ◽  
Neuronal Excitability ◽  
Sodium Current ◽  
Molecular Complexes ◽  
Neuronal Firing ◽  
Signal Integration ◽  
Excitable Cells ◽  
Signalling Molecules ◽  
Voltage Gated Sodium Channels

Currents through voltage-gated sodium channels drive action potential depolarization in neurons and other excitable cells. Smaller currents through these channels are key components of currents that control neuronal firing and signal integration. Changes in sodium current have profound effects on neuronal firing. Sodium channels are controlled by neuromodulators acting through phosphorylation of the channel by serine/threonine and tyrosine protein kinases. That phosphorylation requires specific molecular interaction of kinases and phosphatases with the channel molecule to form localized signalling complexes. Such localization is required for effective neurotransmitter-mediated regulation of sodium channels by protein kinase A. Analogous molecular complexes between sodium channels, kinases and other signalling molecules are expected to be necessary for specific and localized transmitter-mediated modulation of sodium channels by other protein kinases.

scholarly journals Action Potentials and Na+ voltage-gated ion channels in Placozoa

2020 ◽  
Author(s):  
Daria Y. Romanova ◽  
Ivan V. Smirnov ◽  
Mikhail A. Nikitin ◽  
Andrea B. Kohn ◽  
Alisa I. Borman ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Parallel Evolution ◽  
Cell Types ◽  
List Type ◽  
Behavioral Integration ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Invertebrate Animal ◽  
Sodium Dependent

AbstractPlacozoa are small disc-shaped animals, representing the simplest known, possibly ancestral, organization of free-living animals. With only six morphological distinct cell types, without any recognized neurons or muscle, placozoans exhibit fast effector reactions and complex behaviors. However, little is known about electrogenic mechanisms in these animals. Here, we showed the presence of rapid action potentials in four species of placozoans (Trichoplax adhaerens [H1 haplotype], Trichoplax sp.[H2], Hoilungia hongkongensis [H13], and Hoilungia sp. [H4]). These action potentials are sodium-dependent and can be inducible. The molecular analysis suggests the presence of 5-7 different types of voltage-gated sodium channels, which showed substantial evolutionary radiation compared to many other metazoans. Such unexpected diversity of sodium channels in early-branched animal lineages reflect both duplication events and parallel evolution of unique behavioral integration in these nerveless animals.HighlightsPlacozoans are the simplest known animals without recognized neurons and musclesWith only six morphological cell types, placozoans showed complex & rapid behaviorsSodium-dependent action potentials have been discovered in intact animalsVoltage-gated sodium channels (Nav) in Placozoa support a rapid behavioral integrationPlacozoans have more Nav channels that any studied invertebrate animal so farDiversification of Nav-channels highlight the unique evolution of these nerveless animals

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