We hypothesized that the presynaptic Ca(2+)-sensing receptor (CaSR) may contribute to aminoglycoside-induced weakness due to its role in modulating synaptic transmission and its sensitivity to aminoglycosides in heterologous expression systems. We have previously shown that presynaptic CaSR controls a non-selective cation channel (NSCC) that regulates nerve terminal excitability and transmitter release. Using direct, electrophysiological recording, we MK-4827 report that neuronal

VACCs are inhibited by neomycin (IC(50) 830 +/- 10 mu M) at a much lower affinity than CaSR-modulated NSCC currents recorded from acutely isolated presynaptic terminals (synaptosomes; IC(50) 20 +/- 1 mu M). Thus, at clinically relevant concentrations, aminoglycoside-induced weakness is likely precipitated by enhanced CaSR activation and subsequent www.selleckchem.com/products/E7080.html decrease in terminal excitability rather than through direct inhibition of VACCs themselves. (C) 2009 Elsevier Ltd. All rights reserved.”
“The problem of reliability of the dynamics in biological regulatory networks is studied in the framework of a generalized Boolean network model with continuous timing and noise. Using well-known artificial genetic networks such as the repressilator, we discuss concepts of reliability of rhythmic attractors. In a simple evolution process we investigate how overall network structure affects

the reliability of the dynamics. In the course of the evolution, networks are selected for reliable dynamics. We find that most networks can be easily evolved towards reliable functioning while preserving the original function. (c) 2009 Elsevier Ltd. All rights DOK2 reserved.”
“In our previous studies, we have identified that histamine (HA) is co-released with noradrenaline (NA) from the sympathetic nerve terminals and acts as a novel sympathetic neurotransmitter. However, the modulation of sympathetic HA release by sympathetic prejunctional receptors is still unknown. Therefore, in this study, we explored the modulation effect Of alpha(2) adrenoceptors on sympathetic HA release and the interaction of alpha(2)

adrenoceptors with HA H(3) receptors in vas deferens isolated from guinea pig. The selective alpha(2) adrenoceptor agonist brimonidine decreased the HA overflow in a concentration-dependent manner and abolished the contractile responses mediated by sympathetic HA release. Yohimbine competitively blocked the effect of brimonidine on HA release. Similarly, the HA H(3) receptor agonist R-(alpha)-methylhistamine also decreased HA release, and thioperamide blocked the effect of R-(alpha)-methyl-histamine. When used singly, both yohimbine and thioperamide facilitated HA release. In addition, the inhibitory effect of brimonidine on HA release was stronger in the presence of thioperamide, while it was reduced when HA H(3) receptors were activated by R-(alpha)-methylhistamine.