The 32nd Ion Channels Meeting, 17th-20th September 2023, Sète, France.

The 32nd Ion Channel Meetings were organized by the Ion Channels Association from September 17 to 20, 2023 in the Occitanie region (Sète). Researchers, post-docs and students from France, Europe and non-European countries came together to present and discuss their work on various themes covering the field of neuroscience, stem cells, hypoxia and pathophysiology cardiac. Through the plenary conference given by Professor Emilio Carbone and the 5 conferences organized by the scientific committee, attention was paid this year to autism, neuromotor and cardiac disorders and tumor aggressive processes.

Differential effect of Fas activation on spinal muscular atrophy motoneuron death and induction of axonal growth.

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common motoneuron diseases affecting adults and infants, respectively. ALS and SMA are both characterized by the selective degeneration of motoneurons. Although different in their genetic etiology, growing evidence indicates that they share molecular and cellular pathogenic signatures that constitute potential common therapeutic targets.

The Secretome of Human Dental Pulp Stem Cells and Its Components GDF15 and HB-EGF Protect Amyotrophic Lateral Sclerosis Motoneurons against Death.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable paralytic disorder caused by the progressive death of upper and lower motoneurons. Although numerous strategies have been developed to slow disease progression and improve life quality, to date only a few therapeutic treatments are available with still unsatisfactory therapeutic benefits. The secretome of dental pulp stem cells (DPSCs) contains numerous neurotrophic factors that could promote motoneuron survival.

Novel roles for voltage-gated T-type Ca and ClC-2 channels in phagocytosis and angiogenic factor balance identified in human iPSC-derived RPE.

Human-induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure correct data readouts and clinical safety. Previous studies have validated hiPSC-derived RPE as morphologically characteristic of the tissue in the human eye.

Expression of ALS-linked SOD1 Mutation in Motoneurons or Myotubes Induces Differential Effects on Neuromuscular Function In vitro.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects upper and lower motoneurons. Dismantlement of the neuromuscular junction (NMJ) is an early pathological hallmark of the disease whose cellular origin remains still debated. We developed an in vitro NMJ model to investigate the differential contribution of motoneurons and muscle cells expressing ALS-causing mutation in the superoxide dismutase 1 (SOD1) to neuromuscular dysfunction.

Spinal Motoneuron TMEM16F Acts at C-boutons to Modulate Motor Resistance and Contributes to ALS Pathogenesis.

Neuronal Ca entry elicited by electrical activity contributes to information coding via activation of K and Cl channels. While Ca-dependent K channels have been extensively studied, the molecular identity and role of Ca-activated Cl channels (CaCCs) remain unclear. Here, we demonstrate that TMEM16F governs a Ca-activated Cl conductance in spinal motoneurons.

Myotube elasticity of an amyotrophic lateral sclerosis mouse model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor system leading to generalized paralysis and death of patients. The understanding of early pathogenic mechanisms will help to define early diagnostics criteria that will eventually provide basis for efficient therapeutics. Early symptoms of ALS usually include muscle weakness or stiffness.

KCC3-dependent chloride extrusion in adult sensory neurons.

The cation-Cl(-) cotransporters participate to neuronal Cl(-) balance and are responsible for the post-natal Cl(-) switch in central neurons. In the adult peripheral nervous system, it is not well established whether a Cl(-) transition occurs during maturation. We investigated the contribution of cation-Cl(-) cotransporters in the Cl(-) handling of sensory neurons derived from the dorsal root ganglia (DRG) of neonatal mice (postnatal days 1-6) and adult mice.

Neurotrophin-4 modulates the mechanotransducer Cav3.2 T-type calcium current in mice down-hair neurons.

The T-type Ca2+ channel Cav3.2 is expressed in nociceptive and mechanosensitive sensory neurons. The mechanosensitive D-hair (down-hair) neurons, which innervate hair follicles, are characterized by a large-amplitude Cav3.

Development of a sublingual allergy vaccine for grass pollinosis.

Grass pollen is a very common cause of allergic rhinitis and asthma. The only treatment targeting the underlying causes of allergy is immunotherapy (IT). Sublingual immunotherapy (SLIT) has been introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT).

Adherence issues related to sublingual immunotherapy as perceived by allergists.

Objectives: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern.

Best1 is a gene regulated by nerve injury and required for Ca2+-activated Cl- current expression in axotomized sensory neurons.

We investigated the molecular determinants of Ca(2+)-activated chloride current (CaCC) expressed in adult sensory neurons after a nerve injury. Dorsal root ganglia express the transcripts of three gene families known to induce CaCCs in heterologous systems: bestrophin, tweety, and TMEM16. We found with quantitative transcriptional analysis and in situ hybridization that nerve injury induced upregulation of solely bestrophin-1 transcripts in sensory neurons.

The Cav3.2/alpha1H T-type Ca2+ current is a molecular determinant of excitatory effects of GABA in adult sensory neurons.

In addition to its inhibitory action, reports have shown that, in sensory neurons, GABA can be responsible for excitatory effects leading to painful behavior. The cellular mechanisms for these excitatory effects remain largely unknown. Although the high intracellular chloride concentration allows GABA(A) receptor activation to depolarize all adult sensory neurons, we show that GABA, acting through GABA(A) receptors, can generate, in vitro, action potential and intracellular Ca(2+) increase only in a subset of neurons expressing a prominent T-type Ca(2+) current.

NKCC1 phosphorylation stimulates neurite growth of injured adult sensory neurons.

Peripheral nerve section promotes regenerative, elongated neuritic growth of adult sensory neurons. Although the role of chloride homeostasis, through the regulation of ionotropic GABA receptors, in the growth status of immature neurons in the CNS begins to emerge, nothing is known of its role in the regenerative growth of injured adult neurons. To analyze the intracellular Cl- variation after a sciatic nerve section in vivo, gramicidin perforated-patch recordings were used to study muscimol-induced currents in mice dorsal root ganglion neurons isolated from control and axotomized neurons.

K(+) current regulates calcium-activated chloride current-induced after depolarization in axotomized sensory neurons.

One of the major electrophysiological effects of axotomy is a hyperexcitability of injured afferents that is thought to be involved in peripheral neuropathic pain. The molecular determinants of injured sensory neuron excitability are complex and not all have been identified. We have previously shown that sciatic nerve section upregulates the Ca(2+)-activated Cl(-) current in subsets of medium and large sensory neurons.

Calcium dependence of axotomized sensory neurons excitability.

Hyperexcitability of axotomized dorsal root ganglion neurons is thought to play a role in neuropathic pain. Numerous changes in ionic channels expression or current amplitude are reported after an axotomy, but to date no direct correlation between excitability of axotomized sensory neurons and ionic channels alteration has been provided. Following sciatic nerve injury, we examined, under whole-cell patch clamp recording, the effects of calcium homeostasis on the electrical activity of axotomized medium-sized sensory neurons isolated from lumbar dorsal root ganglia of adult mice.