Neuronal Roles of the Multifunctional Protein Dipeptidyl Peptidase-like 6 (DPP6).

The concerted action of voltage-gated ion channels in the brain is fundamental in controlling neuronal physiology and circuit function. Ion channels often associate in multi-protein complexes together with auxiliary subunits, which can strongly influence channel expression and function and, therefore, neuronal computation. One such auxiliary subunit that displays prominent expression in multiple brain regions is the Dipeptidyl aminopeptidase-like protein 6 (DPP6).

Cushing Syndrome in a Pediatric Patient With a KCNJ5 Variant and Successful Treatment With Low-dose Ketoconazole.

Context: Pathogenic variants in KCNJ5, encoding the GIRK4 (Kir3.4) potassium channel, have been implicated in the pathogenesis of familial hyperaldosteronism type-III (FH-III) and sporadic primary aldosteronism (PA). In addition to aldosterone, glucocorticoids are often found elevated in PA in association with KCNJ5 pathogenic variants, albeit at subclinical levels.

P38 Regulates Kainic Acid-Induced Seizure and Neuronal Firing via Kv4.2 Phosphorylation.

The subthreshold, transient A-type K current is a vital regulator of the excitability of neurons throughout the brain. In mammalian hippocampal pyramidal neurons, this current is carried primarily by ion channels comprising Kv4.2 α-subunits.

Activity-dependent isomerization of Kv4.2 by Pin1 regulates cognitive flexibility.

Voltage-gated K channels function in macromolecular complexes with accessory subunits to regulate brain function. Here, we describe a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1)-dependent mechanism that regulates the association of the A-type K channel subunit Kv4.2 with its auxiliary subunit dipeptidyl peptidase 6 (DPP6), and thereby modulates neuronal excitability and cognitive flexibility.

Pharmacological identification of cholinergic receptor subtypes: modulation of locomotion and neural circuit excitability in Drosophila larvae.

Acetylcholine (ACh) is an abundant neurotransmitter and neuromodulator in many species. In Drosophila melanogaster ACh is the neurotransmitter used in peripheral sensory neurons and is a primary excitatory neurotransmitter and neuromodulator within the central nervous system (CNS). The receptors that facilitate cholinergic transmission are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors (nAChRs) and the metabotropic muscarinic acetylcholine receptors (mAChRs).

The effects of potassium and muscle homogenate on proprioceptive responses in crayfish and crab.

Proprioception of limbs and joints is a basic sensory function throughout most of the animal kingdom. It is important to understand how proprioceptive organs and the associated sensory neurons function with altered environments such as increased potassium ion concentrations ([K]) from diseased states, ionic imbalances, and damaged tissues. These factors can drastically alter neuronal activity.

Considerations in repetitive activation of light sensitive ion channels for long-term studies: Channel rhodopsin in the Drosophila model.

Optogenetics is a technique used in various animal models and holds a potential for therapeutic possibilities in mammals. There are technical issues with the use of light sensitive ion channels: reproducible effects over time, controlling where the non-native proteins are targeted within the cell and changes in the biophysical properties of the cells they are expressed in. We used a variant of channel rhodopsin (ChR2-XXL) and targeted expression in neurons of larval Drosophila to investigate the acute and chronic activation, with light pulses, of the channels on synaptic function.

Using optogenetics to assess neuroendocrine modulation of heart rate in Drosophila melanogaster larvae.

The Drosophila melanogaster heart has become a principal model in which to study cardiac physiology and development. While the morphology of the heart in Drosophila and mammals is different, many of the molecular mechanisms that underlie heart development and function are similar and function can be assessed by similar physiological measurements, such as cardiac output, rate, and time in systole or diastole. Here, we have utilized an intact, optogenetic approach to assess the neural influence on heart rate in the third instar larvae.

Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects.