Shift In Steady-state Activation Curve Research Articles

Early exposure to sevoflurane inhibits Ca2+ channels activity in hippocampal CA1 pyramidal neurons of developing rats

Sevoflurane is one of inhalation anesthetics and has been commonly used in obstetric and pediatric anesthesia. The widespread use of sevoflurane in newborns and infants has made its safety a health issue of concern. Voltage-gated Ca2+ channels (VGCCs) play an important role in neuronal excitability and are essential for normal brain development. However, the role of sevoflurane on regulating Ca2+ channels during the period of rapid brain development is still not well understood.The aim of this study is to explore the effects of sevoflurane on voltage-gated Ca2+ channels for hippocampal CA1 pyramidal neurons during the period of rapid brain development. 1-week-old Sprague-Dawley rats were randomly divided into 3 groups: control group, 2.1% sevoflurane group (exposed to 2.1% sevoflurane for 6h) and 3% sevoflurane group (exposed to 3% sevoflurane for 6h). Whole-cell patch clamp technique was used. I–V curve, steady-state activation and inactivation curves of Ca2+ channels were studied in rats of the both 3 treated groups at 5 different ages (1 week, 2 weeks, 3 weeks, 4 and 5 weeks old).After anesthesia with sevoflurane at 1-week-old rats, Ca2+ channels current density was significantly decreased at week 1 and week 2 (p<0.01). And 3% sevoflurane exposure resulted in a rightward shift in steady-state activation curve at week 1 and week 2, as well as the inactivation curve from week 1 to week 3. However, the 2.1% sevoflurane-induced rightward shift was only found in steady-state inactivation curve of Ca2+ channels at week 1 and week 2. Both the slope factor (k) of Ca2+ channels activation and inactivation curves increased by 3% sevoflurane at week 1 (p<0.05).Therefore, early exposure to sevoflurane persistently inhibits Ca2+ channels activity in hippocampal CA1 pyramidal neurons of developing rats but the development of Ca2+ channels recovers to normal level at juvenile age. Moreover, the inhibition of 3% sevoflurane on VGCCs is greater than that of 2.1% sevoflurane.

Electrophysiological properties of delayed rectifier outward K+ currents in the differentiation and development of hippocampal neural stem cells

To study the developmental electrophysiological properties of delayed rectifier outward K+ currents (IDR) in undifferentiated NSC and NSC-derived neurons at various time points of adult SD rat hippocampus in vitro. Neural stem cells were isolated from the hippocampus of adult SD rats with serum-free incubation and single-cell cloning technique. Electrophysiological recordings of IDR were performed using whole-cell patch clamp. The current density of IDR increased in NSC-derived neurons DIV 0-6 d whereas remained constant in DIV > 6 d. The current density of IDR at +50 mV was 45 pA/pF +/- 4 pA/pF and 56 pA/pF +/- 10 pA/pF in undifferentiated NSCs and NSC-derived neurons DIV 0-6 d respectively (n = 9). The activation process of IDR was also altered in DIV 0-6 d whereas remained constant in DIV > 6 d. The positive shift in steady-state activation curve of IDR revealed an increase of V1/2, however the slope factors K remained unchanged. V1/2 was 9 mV +/- 3 mV and 12 mV +/- 3 mV in undifferentiated NSCs and NSC-derived neurons DIV 0-6 d respectively (n = 9, P < 0.05). The inactivation properties of IDR were not altered before and after differentiation. Electrophysiological characteristics of IDR were all altered in DIV 0-6 d, suggesting the essential role of IDR in neurogenesis and early stage of differentiation/development process is very important for the functional mature of neuron.

Link Between SCN5A Mutation and the Brugada Syndrome ECG Phenotype Simulation Study

The specific changes in the gating kinetics of the sodium current (I(Na)) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of I(Na) on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Miyoshi-I(CaL) was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in I(Na) kinetics were made: (1) a-10 mV shift in steady-state inactivation, (2) a+10 mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the I(Na)-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. In this one-dimension model with Ito-density dispersion, DEC-I(Na) precipitates I(Na)-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-I(Na). Concomitant conduction disturbance may be required to cause P2R at physiological Ito density.