Histamine and Corticosterone Modulate Acid Sensing Ion Channels (ASICs) Dependent Long-term Potentiation at the Mouse Anterior Cingulate Cortex.

Increase in proton concentration [H] or decrease in local and global extracellular pH occurs in both physiological and pathological conditions. Acid-sensing ion channels (ASICs), belonging to the ENaC/Deg superfamily, play an important role in signal transduction as proton sensor. ASICs and in particular ASIC1a (one of the six ASICs subunits) which is permeable to Ca, are involved in many physiological processes including synaptic plasticity and neurodegenerative diseases.

Simultaneous administration of cocaine and caffeine dysregulates HCN and T-type channels.

Rationale: The abuse of psychostimulants has adverse consequences on the physiology of the central nervous system. In Argentina, and other South American countries, coca paste or "PACO" (cocaine and caffeine are its major components) is massively consumed with deleterious clinical consequences for the health and well-being of the general population. A scant number of studies have addressed the consequences of stimulant combination of cocaine and caffeine on the physiology of the somatosensory thalamocortical (ThCo) system.

Synaptic signals mediated by protons and acid-sensing ion channels.

Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca currents through multivesicular release in ribbon-type synapses is a proven phenomenon.

Modulation of acid sensing ion channel dependent protonergic neurotransmission at the mouse calyx of Held.

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. It has been reported that homomeric ASIC-1a channels are expressed in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. During synaptic transmission, acidification of the synaptic cleft presumably due to the co-release of neurotransmitter and H from synaptic vesicles activates postsynaptic ASIC-1a channels in mice up to 3 weeks old.

Acid-Sensing Ion Channels Activated by Evoked Released Protons Modulate Synaptic Transmission at the Mouse Calyx of Held Synapse.

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward ASIC currents (Is) in postsynaptic MNTB neurons from wild-type mice.

ASIC channel inhibition enhances excitotoxic neuronal death in an in vitro model of spinal cord injury.

In the spinal cord high extracellular glutamate evokes excitotoxic damage with neuronal loss and severe locomotor impairment. During the cell dysfunction process, extracellular pH becomes acid and may activate acid-sensing ion channels (ASICs) which could be important contributors to neurodegenerative pathologies. Our previous studies have shown that transient application of the glutamate analog kainate (KA) evokes delayed excitotoxic death of spinal neurons, while white matter is mainly spared.

Familial hemiplegic migraine type-1 mutated cav2.1 calcium channels alter inhibitory and excitatory synaptic transmission in the lateral superior olive of mice.

CaV2.1 Ca(2+) channels play a key role in triggering neurotransmitter release and mediating synaptic transmission. Familial hemiplegic migraine type-1 (FHM-1) is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.

Synaptic gain-of-function effects of mutant Cav2.1 channels in a mouse model of familial hemiplegic migraine are due to increased basal [Ca2+]i.

Specific missense mutations in the CACNA1A gene, which encodes a subunit of voltage-gated CaV2.1 channels, are associated with familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of common migraine with aura. We used transgenic knock-in (KI) mice harboring the human pathogenic FHM1 mutation S218L to study presynaptic Ca(2+) currents, EPSCs, and in vivo activity at the calyx of Held synapse.

Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models.

One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological diseases. This review addresses the mutations underlying familial hemiplegic migraine (FHM) with particular interest in Cav2.

Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice.

Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, has been described to have a postsynaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High-frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue.

Presynaptic CaV2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held.

Ca(V)2.1 Ca(2+) channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α(1A) pore-forming subunit of Ca(V)2.

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis.

Studies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. In this review we focus on the role of mutated CaV2.1 (i.

Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of ca(v)2.1 calcium channels.

In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.

Acute modulation of calcium currents and synaptic transmission by gabapentinoids.

Gabapentin and pregabalin are anticonvulsant drugs that are extensively used for the treatment of several neurological and psychiatric disorders. Gabapentinoids (GBPs) are known to have a high affinity binding to α2δ-1 and α2δ-2 auxiliary subunit of specific voltage-gated calcium channels. Despite the confusing effects reported on Ca (2+) currents, most of the studies showed that GBPs reduced release of various neurotransmitters from synapses in several neuronal tissues.

Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential.

Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the alpha(1A) pore-forming subunit of Ca(V)2.1 Ca(2+) channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs).

Changes in synaptic transmission properties due to the expression of N-type calcium channels at the calyx of Held synapse of mice lacking P/Q-type calcium channels.

P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmitting central synapses, but the reasons for the specific expression of one or the other in each particular synapse are not known. Using whole-cell patch clamping from in vitro slices of the auditory brainstem we have examined presynaptic calcium currents (I(pCa)) and glutamatergic excitatory postsynaptic currents (EPSCs) at the calyx of Held synapse from transgenic mice in which the alpha(1A) pore-forming subunit of the P/Q-type Ca(2+) channels is ablated (KO). The power relationship between Ca(2+) influx and quantal output was studied by varying the number of Ca(2+) channels engaged in triggering release.

Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of Held presynaptic terminal.

Calcium channels of the P/Q subtype mediate transmitter release at the neuromuscular junction and at many central synapses, such as the calyx of Held. Transgenic mice in which alpha1A channels are ablated provide a powerful tool with which to test compensatory mechanisms at the synapse and to explore mechanisms of presynaptic regulation associated with expression of P/Q channels. Using the calyx of Held preparation from the knock-out (KO) mice, we show here that N-type channels functionally compensate for the absence of P/Q subunits at the calyx and evoke giant synaptic currents [approximately two-thirds of the magnitude of wild-type (WT) responses].