Membrane Excitability and Disease

Author(s):  
Bruce Hendry
2003 ◽  
Vol 773 ◽  
Author(s):  
Mo Yang ◽  
Shalini Prasad ◽  
Xuan Zhang ◽  
Mihrimah Ozkan ◽  
Cengiz S. Ozkan

AbstractExtracellular potential is an important parameter which indicates the electrical activity of live cells. Membrane excitability in osteoblasts plays a key role in modulating the electrical activity in the presence of chemical agents. The complexity of cell signal makes interpretation of the cellular response to a chemical agent very difficult. By analyzing shifts in the signal power spectrum, it is possible to determine a frequency spectrum also known as Signature Pattern Vectors (SPV) specific to a chemical. It is also essential to characterize single cell sensitivity and response time for specific chemical agents for developing detect-to-warn biosensors. We used a 4x4 multiple Pt microelectrode array to spatially position single osteoblast cells, by using a gradient AC field. Fast Fourier Transformation (FFT) and Wavelet Transformation (WT) analyses were used to extract information pertaining to the frequency of firing from the extracellular potential.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingzhao Su ◽  
Junhua Liu ◽  
Baocong Yu ◽  
Kaixing Zhou ◽  
Congli Sun ◽  
...  

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Stuart A Collins ◽  
Ipe Ninan

Abstract The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daisuke Kase ◽  
Keiji Imoto

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.


Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S53
Author(s):  
John Santucci ◽  
Xianming Lin ◽  
Lei Bu ◽  
Naoko Yamaguchi ◽  
Akshay Shekhar ◽  
...  

1986 ◽  
Vol 55 (3) ◽  
pp. 449-468 ◽  
Author(s):  
T. Sakamoto ◽  
Y. Atsuta ◽  
S. Mori

Stimulation of the dorsal portion of the caudal tegmental field (DTF) in the pons resulted in hyperpolarization of extensor alpha-motoneurons (alpha-MNs) that persisted for several minutes after cessation of the stimulation. The resulting inhibition of alpha-MN discharge led to a progressive reduction in the number of active motor units. Renshaw cells, persistently active at high levels of extensor muscle tone, were abruptly silenced by DTF stimulation. Active discharge was renewed at the time of cessation of the stimulation but at a frequency reduced in proportion to the persistently lowered level of extensor muscle tone. Ia primary afferents were tonically active during the high extensor tonus of reflex standing. DTF stimulation was accompanied by a brief, slight increase in Ia discharge frequency followed by a reduction in frequency variably correlated to the magnitude of extensor force reduction. Orthodromically elicited Ia EPSPs in the soleus alpha-MNs were reduced in peak voltage, time to peak, and half width during the hyperpolarization accompanying DTF stimulation. All of these parameters recovered beyond their prestimulus values with the cessation of DTF stimulation in spite of the persisting hyperpolarization. Antidromically initiated invasion of the somatodendritic (SD) segment of the motoneuron membrane was delayed and sometimes blocked during DTF stimulation. At the same time, the peak voltage of the SD action potential was reduced. There was an immediate recovery of these changes on termination of DTF stimulation, although the poststimulus hyperpolarization persisted. Intracellular injection of depolarizing current steps during DTF stimulation revealed a depression of membrane excitability that persisted during the hyperpolarization that followed the termination of the DTF stimulation. Depolarizing and hyperpolarizing steps of intracellular current were used to demonstrate a reduction of cellular input resistance during DTF stimulation. The resistance values rapidly returned to prestimulus levels following the cessation of DTF stimulation. It was demonstrated that the degree of resistance change is greater and that the magnitude of DTF-induced hyperpolarization is smaller for low-resistance cells than for high-resistance cells. Iontophoretically induced increase in intracellular Cl- resulted in a reversal of both Ia IPSPs and the hyperpolarization induced by DTF stimulation. The hyperpolarization enduring after DTF stimulation was not affected by the Cl- injection.


2008 ◽  
Vol 100 (4) ◽  
pp. 1897-1908 ◽  
Author(s):  
Wendy W. Wu ◽  
C. Savio Chan ◽  
D. James Surmeier ◽  
John F. Disterhoft

Experience-dependent modification in the electrical properties of central neurons is a form of intrinsic plasticity that occurs during development and has been observed following behavioral learning. We report a novel form of intrinsic plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train (30 Hz, 3 s) potentiated the KV7/KCNQ channel function and led to a long-lasting, activity-dependent increase in spike frequency adaptation—a gradual reduction in the firing frequency in response to sustained excitation. These effects were abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca2+ influx and subsequent activation of PKA on KV7/KCNQ channels may represent a generalized principle in fine tuning the output of central neurons that promotes stability in firing—an example of homeostatic regulation of intrinsic membrane excitability.


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