Neuroscience_topics
Follow
Find tag "Electrophysiology"
17.2K views | +0 today
Neuroscience_topics
Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
Your new post is loading...
Your new post is loading...
Scooped by Julien Hering, PhD
Scoop.it!

Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction

Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction | Neuroscience_topics | Scoop.it

[Review] Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due to multiple genes that encode calcium channel α1 subunits, coassembly with a variety of ancillary calcium channel subunits, and alternative splicing. This allows these channels to fulfill highly specialized roles in specific neuronal subtypes and at particular subcellular loci. While calcium channels are of critical importance to brain function, their inappropriate expression or dysfunction gives rise to a variety of neurological disorders, including, pain, epilepsy, migraine, and ataxia. This Review discusses salient aspects of voltage-gated calcium channel function, physiology, and pathophysiology. - by Simms BA & Zamponi GW, Neuron, Volume 82, Issue 1, p24–45, 2 April 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Therapeutic potential of NaV1.1 activators

Highlights:- NaV1.1 is the major sodium current in specific inhibitory interneurons.- Interneuronal dysfunction is linked to epilepsies, schizophrenia, and AD.- NaV1.1 plays a modest role in excitatory neurons.- Selective NaV1.1 activators may hold great potential as a novel treatment paradigm.

By Jensen HS et al.,  Trends in Pharmacological Sciences, Volume 35, Issue 3, p113–118, March 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Ligand-Gating by Ca2+ Is Rate Limiting for Physiological Operation of BKCa Channels

Large conductance Ca2+- and voltage-activated potassium channels (BKCa) shape neuronal excitability and signal transduction. This reflects the integrated influences of transmembrane voltage and intracellular calcium concentration ([Ca2+]i) that gate the channels. This dual gating has been mainly studied as voltage-triggered gating modulated by defined steady-state [Ca2+]i, a paradigm that does not approximate native conditions. Here we use submillisecond changes of [Ca2+]i to investigate the time course of the Ca2+-triggered gating of BKCa channels expressed in Chinese hamster ovary cells at distinct membrane potentials in the physiological range. The results show that Ca2+ can effectively gate BKCa channels and that Ca2+ gating is largely different from voltage-driven gating. Most prominently, Ca2+ gating displays a pronounced delay in the millisecond range between Ca2+ application and channel opening (pre-onset delay) and exhibits slower kinetics across the entire [Ca2+]i-voltage plane. Both characteristics are selectively altered by co-assembled BKβ4 or an epilepsy-causing mutation that either slows deactivation or speeds activation and reduces the pre-onset delay, respectively. Similarly, co-assembly of the BKCachannels with voltage-activated Ca2+ (Cav) channels, mirroring the native configuration, decreased the pre-onset delay to submillisecond values. In BKCa–Cav complexes, the time course of the hyperpolarizing K+-current response is dictated by the Ca2+ gating of the BKCa channels. Consistent with Cav-mediated Ca2+ influx, gating was fastest at hyperpolarized potentials, but decreased with depolarization of the membrane potential. Our results demonstrate that under experimental paradigms meant to approximate the physiological conditions BKCa channels primarily operate as ligand-activated channels gated by intracellular Ca2+ and that Ca2+ gating is tuned for fast responses in neuronal BKCa–Cav complexes. - by Berkefeld H & Fakler B, The Journal of Neuroscience, 24 April 2013, 33(17): 7358-7367

Julien Hering, PhD's insight:

The BKca channels are directly tuned by intracellular calcium binding. These channels are fast-operated by variation of intracellular calcium in physiological conditions through the BKca-Cav complexes.

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Kv7 channels as targets for anti-epileptic and psychiatric drug-development

Kv7 channels as targets for anti-epileptic and psychiatric drug-development | Neuroscience_topics | Scoop.it
The Kv7 channels, a family of voltage-dependent K+ channels (Kv7.1–Kv7.5), have gained much attention in drug discovery especially because four members are genetically linked to diseases. For disorders of the CNS focus was originally on epilepsy and pain, but it is becoming increasingly evident that Kv7 channels can also be valid targets for psychiatric disorders, such as anxiety and mania. The common denominator is probably neuronal hyperexcitability in different brain areas, which can be successfully attenuated by pharmacological increment of Kv7 channel activity. This perspective attempts to review the current status and challenges for CNS drug discovery based on Kv7 channels as targets for neurological and psychiatric indications with special focus on selectivity and mode-of-actions. - by Grunnet M. et al., European Journal of Pharmacology, Volume 726, 5 March 2014, Pages 133–137
more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neurophysiology of HCN channels: From cellular functions to multiple regulations

Neurophysiology of HCN channels: From cellular functions to multiple regulations | Neuroscience_topics | Scoop.it
Highlights
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are involved in multiple physiological processes.
  • HCN channels are excellent targets of various cellular signals to finely regulate neuronal responses to external stimuli.
  • Dysregulation of HCN channels is involved in a variety of neurological disorders.
by He C et al.Progress in NeurobiologyVolume 112, January 2014, Pages 1–23
Julien Hering, PhD's insight:

An interesting review about HCN these must-known ion channels that are involved in numerous physiological processes and brain diseases.

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

NMDA and GABAB (KIR) Conductances: The “Perfect Couple” for Bistability

[Abstract] Networks that produce persistent firing in response to novel input patterns are thought to be important in working memory and other information storage functions. One possible mechanism for maintaining persistent firing is dendritic voltage bistability in which the depolarized state depends on the voltage dependence of the NMDA conductance at recurrent synapses. In previous models, the hyperpolarized state is dependent on voltage-independent conductances, including GABAA. The interplay of these conductances leads to bistability, but its robustness is limited by the fact that the conductance ratio must be within a narrow range. The GABAB component of inhibitory transmission was not considered in previous analyses. Here, we show that the voltage dependence of the inwardly rectifying potassium (KIR) conductance activated by GABAB receptors adds substantial robustness to network simulations of bistability and the persistent firing that it underlies. The hyperpolarized state is robust because, at hyperpolarized potentials, the GABAB/KIR conductance is high and the NMDA conductance is low; the depolarized state is robust because, at depolarized potentials, the NMDA conductance is high and the GABAB/KIR conductance is low. Our results suggest that this complementary voltage dependence of GABAB/KIR and NMDA conductances makes them a “perfect couple” for producing voltage bistability. - Sanders H. et al., The Journal of Neuroscience, 9 January 2013, 33(2): 424-429

Julien Hering, PhD's insight:

The NMDA/GABAB receptor channels bipolar couple is perfect to generate bistability in a narrow window of voltage. 

more...
No comment yet.