Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders.

A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs) are multipotent stem cells that reside deep the pulp of shed teeth.

Variation in Dube3a expression affects neurotransmission at the Drosophila neuromuscular junction.

Changes in UBE3A expression levels in neurons can cause neurogenetic disorders ranging from Angelman syndrome (AS) (decreased levels) to autism (increased levels). Here we investigated the effects on neuronal function of varying UBE3A levels using the Drosophila neuromuscular junction as a model for both of these neurogenetic disorders. Stimulations that evoked excitatory junction potentials (EJPs) at 1 Hz intermittently failed to evoke EJPs at 15 Hz in a significantly higher proportion of Dube3a over-expressors using the pan neuronal GAL4 driver C155-GAL4 (C155-GAL4>UAS-Dube3a) relative to controls (C155>+ alone).

Variation in sodium current amplitude between vasopressin and oxytocin hypothalamic supraoptic neurons.

Biophysical characteristics of tetrodotoxin-sensitive sodium (Na(+)) currents were studied in vasopressin (VP) and oxytocin (OT) supraoptic neurons acutely isolated from rat hypothalamus. Na(+) current density (pA/pF) was significantly greater in VP neurons than in OT neurons. No significant difference between VP and OT neurons was detected regarding the voltage dependence of activation and steady-state inactivation, or rate of recovery from inactivation of Na(+) currents.

A modeling study of T-type Ca2+ channel gating and modulation by L-cysteine in rat nociceptors.

L-cysteine (L-cys) increases the amplitude of T-type Ca(2+) currents in rat T-rich nociceptor-like dorsal root ganglia neurons. The modulation of T-type Ca(2+) channel gating by L-cys was studied by fitting Markov state models to whole-cell currents recorded from T-rich neurons. The best fitting model tested included three resting states and inactivation from the second resting state and the open state.

Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels.

Carbamazepine was tested on high-threshold TTX-resistant Na+ currents (TTX-R-currents), evoked from acutely isolated rat dorsal root ganglion (DRG) cells. Under control conditions, the TTX-R-currents recorded from different DRG cells varied greatly regarding use-dependent inactivation (TTX-R-current UDI), measured as the percent decrease in current amplitude induced by changing the current activation rate from 0.1 Hz to 1.

Reduced transition between open and inactivated channel states underlies 5HT increased I(Na+) in rat nociceptors.

We previously demonstrated that activation of a 5HT(4) receptor coupled cAMP-dependent signaling pathway increases tetrodotoxin-resistant Na(+) current (I(Na)) in a nociceptor-like subpopulation of rat dorsal root ganglion cells (type 2). In the present study we used electrophysiology experiments and computer modeling studies to explore the mechanism(s) underlying the increase of I(Na) by 5HT. In electrophysiological experiments with type 2 dorsal root ganglion cells, 5HT increased peak I(Na) and the activation and inactivation rate, without significantly affecting the voltage dependency of activation or availability.