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Advances in Physiology Education Mar 2021The ability to understand the relationship between the reversal potential and the membrane potential is a fundamental skill that must be mastered by students studying...
The ability to understand the relationship between the reversal potential and the membrane potential is a fundamental skill that must be mastered by students studying membrane excitability. To clarify this relationship, we have reframed a classic experiment carried out by Hodgkin and Katz, where we compare graphically the membrane potential at three phases of the action potential (resting potential, action potential peak, and afterhyperpolarization) to reversal potential for K (), reversal potential for Na (), and membrane potential () (calculated by the Goldman Hodgkin Katz equation) to illustrate that the membrane potential approaches the reversal potential of the ion to which it is most permeable at that instant.
Topics: Action Potentials; Cell Membrane Permeability; Humans; Membrane Potentials; Models, Biological; Permeability; Potassium
PubMed: 33661050
DOI: 10.1152/advan.00188.2020 -
BMC Research Notes May 2018In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We...
OBJECTIVE
In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a direct role in neuronal excitability. Of the HIV peptides, Tat is secreted and acts in other cells. In order to examine whether the HIV Tat can modify neuronal excitability, we exposed primary murine hippocampal neurons to that peptide, and tested its effects on the intrinsic membrane properties, 4 and 24 h after exposure.
RESULTS
The exposure of hippocampal pyramidal neurons to Tat for 4 h did not alter intrinsic membrane properties. However, we found a strong increase in intrinsic excitability, characterized by increase of the slope (Gain) of the input-output function, in cells treated with Tat for 24 h. Nevertheless, Tat treatment for 24 h did not alter the resting membrane potential, input resistance, rheobase and action potential threshold. Thus, neuronal adaptability to Tat exposure for 24 h is not applicable to basic neuronal properties. A restricted but significant effect on coupling the inputs to the outputs may have implications to our knowledge of Tat biophysical firing capability, and its involvement in neuronal hyperexcitability in neuroHIV.
Topics: Animals; HIV-1; Hippocampus; Membrane Potentials; Mice; Mice, Inbred C57BL; Pyramidal Cells; Recombinant Proteins; Synaptic Transmission; tat Gene Products, Human Immunodeficiency Virus
PubMed: 29728138
DOI: 10.1186/s13104-018-3376-8 -
Physical Review. E Jun 2022Bacteria meticulously regulate their intracellular ion concentrations and create ionic concentration gradients across the bacterial membrane. These ionic concentration...
Bacteria meticulously regulate their intracellular ion concentrations and create ionic concentration gradients across the bacterial membrane. These ionic concentration gradients provide free energy for many cellular processes and are maintained by transmembrane transport. Given the physical dimensions of a bacterium and the stochasticity in transmembrane transport, intracellular ion concentrations and hence the charge state of a bacterium are bound to fluctuate. Here we investigate the charge noise of hundreds of nonmotile bacteria by combining electrical measurement techniques from condensed matter physics with microfluidics. In our experiments, bacteria in a microchannel generate charge density fluctuations in the embedding electrolyte due to random influx and efflux of ions. Detected as electrical resistance noise, these charge density fluctuations display a power spectral density proportional to 1/f^{2} for frequencies 0.05Hz≤f≤1Hz. Fits to a simple noise model suggest that the steady-state charge of a bacterium fluctuates by ±1.30×10^{6}e(e≈1.60×10^{-19}C), indicating that bacterial ion homeostasis is highly dynamic and dominated by strong charge noise. The rms charge noise can then be used to estimate the fluctuations in the membrane potential; however, the estimates are unreliable due to our limited understanding of the intracellular concentration gradients.
Topics: Bacteria; Biological Transport; Cell Physiological Phenomena; Ions; Membrane Potentials
PubMed: 35854507
DOI: 10.1103/PhysRevE.105.064413 -
PloS One 2023Neocortical neurons can increasingly be divided into well-defined classes, but their activity patterns during quantified behavior remain to be fully determined. Here, we...
Neocortical neurons can increasingly be divided into well-defined classes, but their activity patterns during quantified behavior remain to be fully determined. Here, we obtained membrane potential recordings from various classes of excitatory and inhibitory neurons located across different cortical depths in the primary whisker somatosensory barrel cortex of awake head-restrained mice during quiet wakefulness, free whisking and active touch. Excitatory neurons, especially those located superficially, were hyperpolarized with low action potential firing rates relative to inhibitory neurons. Parvalbumin-expressing inhibitory neurons on average fired at the highest rates, responding strongly and rapidly to whisker touch. Vasoactive intestinal peptide-expressing inhibitory neurons were excited during whisking, but responded to active touch only after a delay. Somatostatin-expressing inhibitory neurons had the smallest membrane potential fluctuations and exhibited hyperpolarising responses at whisking onset for superficial, but not deep, neurons. Interestingly, rapid repetitive whisker touch evoked excitatory responses in somatostatin-expressing inhibitory neurons, but not when the intercontact interval was long. Our analyses suggest that distinct genetically-defined classes of neurons at different subpial depths have differential activity patterns depending upon behavioral state providing a basis for constraining future computational models of neocortical function.
Topics: Animals; Membrane Potentials; Vibrissae; Touch; Neurons; Somatostatin
PubMed: 37311008
DOI: 10.1371/journal.pone.0287174 -
ELife Jul 2018The cellular and synaptic mechanisms driving cell-type-specific function during various cortical network activities and behaviors are poorly understood. Here, we...
The cellular and synaptic mechanisms driving cell-type-specific function during various cortical network activities and behaviors are poorly understood. Here, we targeted whole-cell recordings to two classes of inhibitory GABAergic neurons in layer 2/3 of the barrel cortex of awake head-restrained mice and correlated spontaneous membrane potential dynamics with cortical state and whisking behavior. Using optogenetic stimulation of single layer 2/3 excitatory neurons we measured unitary excitatory postsynaptic potentials (uEPSPs) across states. During active states, characterized by whisking and reduced low-frequency activity in the local field potential, parvalbumin-expressing neurons depolarized and, albeit in a small number of recordings, received uEPSPs with increased amplitude. In contrast, somatostatin-expressing neurons hyperpolarized and reduced firing rates during active states without consistent change in uEPSP amplitude. These results further our understanding of neocortical inhibitory neuron function in awake mice and are consistent with the hypothesis that distinct genetically-defined cell classes have different state-dependent patterns of activity.
Topics: Action Potentials; Animals; Female; GABAergic Neurons; Male; Membrane Potentials; Mice; Optogenetics; Somatosensory Cortex; Synaptic Transmission; Vibrissae; Wakefulness
PubMed: 30052198
DOI: 10.7554/eLife.35869 -
Journal of Neural Engineering Jul 2022A new axonal conduction model was used to analyze the interaction between intracellular sodium concentration and membrane potential oscillation in axonal conduction...
A new axonal conduction model was used to analyze the interaction between intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS).The model includes intracellular and extracellular sodium and potassium concentrations and ion pumps. First, the HFBS (1 kHz, 5.4 mA) was applied for a duration (59.4 s) long enough to produce an axonal conduction block after terminating the stimulation, i.e. a post-stimulation block. Then, the intensity of HFBS was reduced to a lower level for 4 s to determine if the axonal conduction block could be maintained.The block duration was shortened from 1363 ms to 5 ms as the reduced HFBS intensity was increased from 0 mA to 4.1 mA. The block was maintained for the entire tested period (4000 ms) if the reduced intensity was above 4.2 mA. At the low intensity (<4.2 mA) the membrane potential oscillation disrupted the post-stimulation block caused by the increased intracellular sodium concentration, while at the high intensity (>4.2 mA) the membrane potential oscillation was strong enough to maintain the block and further increased the intracellular sodium concentration.This study indicates a possibility to develop a new nerve block method to reduce the HFBS intensity, which can extend the battery life for an implantable nerve stimulator in clinical applications to block pain of peripheral origin.
Topics: Action Potentials; Axons; Electric Stimulation; Membrane Potentials; Models, Neurological; Neural Conduction; Sodium
PubMed: 35850095
DOI: 10.1088/1741-2552/ac81ef -
Scientific Reports Sep 2021Even in nonexcitable cells, the membrane potential V is fundamental to cell function, with roles from ion channel regulation, development, to cancer metastasis. V arises...
Even in nonexcitable cells, the membrane potential V is fundamental to cell function, with roles from ion channel regulation, development, to cancer metastasis. V arises from transmembrane ion concentration gradients; standard models assume homogeneous extracellular and intracellular ion concentrations, and that V only exists across the cell membrane and has no significance beyond it. Using red blood cells, we show that this is incorrect, or at least incomplete; V is detectable beyond the cell surface, and modulating V produces quantifiable and consistent changes in extracellular potential. Evidence strongly suggests this is due to capacitive coupling between V and the electrical double layer, rather than molecular transporters. We show that modulating V changes the extracellular ion composition, mimicking the behaviour if voltage-gated ion channels in non-excitable channels. We also observed V-synchronised circadian rhythms in extracellular potential, with significant implications for cell-cell interactions and cardiovascular disease.
Topics: Cell Membrane; Circadian Rhythm; Electrophysiological Phenomena; Erythrocytes; Humans; Membrane Potentials; Neuraminidase; Valinomycin
PubMed: 34593849
DOI: 10.1038/s41598-021-98102-9 -
Nature Communications Dec 2016Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that...
Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.
Topics: Animals; Grasshoppers; Membrane Potentials; Models, Neurological; Models, Theoretical; Mushroom Bodies; Neurons; Noise; Patch-Clamp Techniques; Smell
PubMed: 27976720
DOI: 10.1038/ncomms13808 -
Journal of Neurophysiology Oct 2016Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In...
Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (greater than -40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of L-type calcium currents (Ca1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (Ca2.2) reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. The blocking of any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated anoctamin 2 (ANO2), and not ANO1, as the CaCC source. Biophysical modeling showed that Ca1, Ca2.2, and ANO2 are sufficient to generate a membrane potential oscillation and membrane resonance, similar to that in LTS interneurons. LTS interneurons exhibit a membrane potential oscillation and membrane resonance that are both generated by Ca1 and Ca2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.
Topics: Animals; Calcium Channel Blockers; Corpus Striatum; Green Fluorescent Proteins; Immunohistochemistry; Interneurons; Ion Channels; Membrane Potentials; Mice, Transgenic; Models, Molecular; Models, Neurological; Neuropeptide Y; Neurotransmitter Agents; Patch-Clamp Techniques; Periodicity; Promoter Regions, Genetic; Tissue Culture Techniques
PubMed: 27440246
DOI: 10.1152/jn.00511.2016 -
The Journal of Physiology May 2020Action potential driven neuronal signalling drives several electrical and biochemical processes in the nervous system. However, neurons can maintain synaptic... (Review)
Review
Action potential driven neuronal signalling drives several electrical and biochemical processes in the nervous system. However, neurons can maintain synaptic communication and signalling under resting conditions independently of activity. Importantly, these processes are regulated by Ca signals that occur at rest. Several studies have suggested that opening of voltage-gated Ca channels near resting membrane potentials, activation of NMDA receptors in the absence of depolarization or Ca release from intracellular stores can drive neurotransmitter release as well as subsequent signalling in the absence of action potentials. Interestingly, recent studies have demonstrated that manipulation of resting neuronal Ca signalling yielded pronounced homeostatic synaptic plasticity, suggesting a critical role for this resting form of signalling in regulation of synaptic efficacy and neuronal homeostasis. Given their robust impact on synaptic efficacy and neuronal signalling, neuronal resting Ca signals warrant further mechanistic analysis that includes the potential role of store-operated Ca entry in these processes.
Topics: Action Potentials; Calcium; Membrane Potentials; Neurons; Synaptic Transmission
PubMed: 30735245
DOI: 10.1113/JP276541