A solution-based nano-plasmonic sensing technique by using gold nanorods.

We have successfully demonstrated a novel sensing technique for monitoring the variation of solution concentrations and measuring the effective dielectric constant in a medium by means of an ultra-small and label-free nanosensor, the mechanism of which is based on the localized surface plasmon resonance (LSPR) of gold nanorods. The nanorods are fabricated in a narrow size distribution, which is characterized by transmission electron microscopy and optical absorption spectroscopy. In addition, we employ a simple analytical calculation to examine the LSPR band of the absorption spectrum, which provides excellent consistency with aspect ratio. The plasmonic sensing is performed by detecting the diffusion process and saturation concentration of hexadecyltrimethylammonium bromide in water, and tracing the effective dielectric constants of the medium simultaneously. This promising sensing and analytical technique can be easily used for investigating the nano-scale variations of mixing or reaction process in a micro/nanofluidic channel or the biological interaction in the cytoplasm of the cell.

Beta-adrenergic modulation of arrhythmogenesis and identification of targeted sites of antiarrhythmic therapy in Timothy (LQT8) syndrome: a theoretical study.

Timothy syndrome (TS) is a malignant form of congenital long QT syndrome with a mode of arrhythmia onset often triggered by enhanced sympathetic tone. We sought to explore mechanisms by which beta-adrenergic stimulation (BAS) modulates arrhythmogenesis and to identify potential targeted sites of antiarrhythmic therapy in TS. Using a dynamic Luo-Rudy ventricular myocyte model incorporated with detailed intracellular Ca(2+) cycling, along with its one-dimensional multicellular strand, we simulated various clinical scenarios of TS, with stepwise increase in the percentage of G406R Ca(v)1.2 channels from 0 to 11.5 and 23%, and to 38.5 and 77%, respectively, for heterozygous and homozygous states of TS1 and TS2. Progressive prolongation of action potential duration (APD) and QT interval, accompanied by amplification of transmural dispersion of repolarization, steepening of APD restitution, induction of delayed afterdepolariztions (DADs), and both DAD and phase 3 early afterdepolariztion-mediated triggered activities, correlated well with the extent of G406R Ca(v)1.2 channel mutation. BAS amplified transmural dispersion of repolarization, steepened APD restitution, and facilitated inducibility of DAD-mediated triggered activity. Systematic analysis of intracellular Ca(2+) cycling revealed that sarcoplasmic reticulum Ca(2+) ATPase (uptake current) played an essential role in BAS-induced facilitation of DAD-mediated triggered activity and, in addition to L-type calcium current, it could be an effective site of antiarrhythmic therapy under the influence of BAS. Thus G406R Ca(v)1.2 channel mutation confers not only a trigger, but also a substrate for lethal ventricular arrhythmias, which can be exaggerated by BAS. It is suggested that, besides beta-adrenergic blockers and L-type calcium current channel blockers, an agent aimed at reduction of sarcoplasmic reticulum Ca(2+) ATPase uptake current may provide additional antiarrhythmic effect in patients with TS.

The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells.

Oxaliplatin (OXAL) is a platinum-based chemotherapeutic agent which is effective against advanced or metastatic gastrointestinal cancer. However, the mechanisms responsible for the development of the neuropathy induced by this agent remain unclear. In this study, we attempted to evaluate the possible effects of OXAL on ion currents and action potentials (APs) in NG108-15 cells differentiated with dibutyryl cyclic-AMP. Application of OXAL decreased the peak amplitude of voltage-gated Na(+) current (I(Na)) with no change in the overall current-voltage relations of the currents. This agent also produced a concentration-dependent slowing of I(Na) inactivation. A further application of ranolazine reversed OXAL-induced slowing of I(Na) inactivation. Unlike ranolazine or riluzole, OXAL had no effect on persistent I(Na) elicited by long ramp pulses. OXAL (100 microM) also had little or no effect on the peak amplitude of L-type Ca(2+) currents in NG108-15 cells, while it suppressed delayed-rectifier K(+) current. In current-clamp recordings, OXAL alone reduced the amplitude of APs; however, it did not alter the duration of APs. However, after application of tefluthrin, OXAL did increase the duration of APs. Moreover, OXAL decreased the peak amplitude of I(Na) with a concomitant reduction of current inactivation in HEK293T cells expressing SCN5A. The effects of OXAL on ion currents presented here may contribute to its neurotoxic actions in vivo.

Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells.

The rapidly inactivating (I(Naf)) and noninactivating Na(+) currents (I(Na)(()(NI)())) were characterized in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP in this study. Standard activation and inactivation protocols were used to evaluate the steady-state and kinetic properties of the I(Naf) present in these cells. The voltage protocols with a slowly depolarizing ramp were implemented to examine the properties of I(Na)(()(NI)()). Based on experimental data and computer simulations, a window component of the rapidly inactivating sodium current (I(Naf)(()(W)())) was also generated in response to the slowly depolarizing ramp. The I(Naf)(()(W)()) was subtracted from I(Na)(()(NI)()) to yield the persistent Na(+) current (I(Na)(()(P)())). Our results demonstrate the presence of I(Na)(()(P)()) in these cells. In addition to modifying the steady-state inactivation of I(Naf), ranolazine or riluzloe could be effective in blocking I(Naf)(()(W)()) and I(Na)(()(P)()). The ability of ranolazine and riluzole to suppress I(Na)(()(P)()) was greater than their ability to inhibit I(Naf)(()(W)()). In current-clamp recordings, current-induced voltage oscillations were applied to elicit action potentials (APs) through a gradual transition between spontaneous depolarization and upstroke. Ranolazine or riluzole at a concentration of 3 microM then effectively suppressed the AP firing generated by oscillatory changes in membrane current. The data suggest that a small rise in I(Na)(()(NI)()) facilitates neuronal hyper-excitability due the decreased threshold of AP initiation. The underlying mechanism of the inhibitory actions of ranolazine or riluzole on membrane potential in neurons or neuroendocrine cells in vivo may thus be associated with their blocking of I(Na)(()(NI)()).

Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1-7) neurons.

Tefluthrin is a synthetic pyrethroid and involved in acute neurotoxic effects. How this compound affects ion currents in endocrine or neuroendocrine cells remains unclear. Its effects on membrane ion currents in pituitary tumor (GH3) cells and in hypothalamic (GT1-7) neurons were investigated. Application of Tef (10 microM) increased the amplitude of voltage-gated Na+ current (INa), along with a slowing in current inactivation and deactivation in GH3 cells. The current-voltage relationship of INa was shifted to more negative potentials in the presence of this compound. Tef increased INa with an EC50 value of 3.2 +/- 0.8 microM. It also increased the amplitude of persistent INa. Tef reduced the amplitude of L-type Ca2+ current. This agent slightly inhibited K+ outward current; however, it had no effect on the activity of large-conductance Ca2+-activated K+ channels. Under cell-attached voltage-clamp recordings, Tef (10 microM) increased amplitude and frequency of spontaneous action currents, along with appearance of oscillatory inward currents. Tef-induced inward currents were suppressed after further application of tetrodotoxin, riluzole or ranolazine. In GT1-7 cells, Tef also increased the amplitude and frequency of action currents. Taken together, the effects of Tef and its structural related pyrethroids on ion currents can contribute to the underlying mechanisms through which they affect endocrine or neuroendocrine function in vivo.