Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.

Fever-associated seizures or epilepsy (FASE) is primarily characterised by the occurrence of a seizure or epilepsy usually accompanied by a fever. It is common in infants and children, and generally includes febrile seizures (FS), febrile seizures plus (FS+), Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFSP). The aetiology of FASE is unclear. Genetic factors may play crucial roles in FASE. Mutations in certain genes may cause a wide spectrum of phenotypical overlap ranging from isolated FS, FS+ and GEFSP to DS. Synapse-associated proteins, postsynaptic GABAA receptor, and sodium channels play important roles in synaptic transmission. Mutations in these genes may involve in the pathogenesis of FASE. Elevated temperature promotes synaptic vesicle (SV) recycling and enlarges SV size, which may enhance synaptic transmission and contribute to FASE occurring. This review provides an overview of the loci, genes, underlying pathogenesis and the fever-inducing effect of FASE. It may provide a more comprehensive understanding of pathogenesis and contribute to the clinical diagnosis of FASE.

Populations of Plutella xylostella, extending over 3800 km in southern Australia, show no genetic structure as assessed by microsatellite markers; yet outbreaks of pyrethroid resistance occur sporadically in cropping areas. Since mutations in the para voltage-gated sodium channel gene have been implicated in pyrethroid resistance, we looked for DNA sequence variation at this target among Australian moths. We found two resistance mutations previously reported for this species (L1014F and T929I), as well as a novel substitution (F1020S). Of the eight possible haplotypes formed by combinations of these three biallelic polymorphisms, only four were found in Australian populations: the wild-type allele (w), the kdr mutation allele (kdr) with only L1014F, the super-kdr-like combination of L1014F and T929I (skdrl), and the crashdown allele with only F1020S (cdr). Comparison of genotype frequencies among survivors of permethrin assays with those from untreated controls identified three resistant genotypes: skdrl homozygotes, cdr homozygotes and the corresponding heterozygote, cdr/skrdl – the heterozygote being at least as resistant as either homozygote. Spatial heterogeneity of allele frequencies was conspicuous, both across the continent and among local collections, consistent with reported spatial heterogeneity of pyrethroid resistance. Further, high resistance samples were sometimes associated with high frequency of cdr, sometimes high frequency of skdrl, or sometimes with a high combined cdr+skdrl frequency. The skdrl and cdr alleles explain a high proportion of the Australia-wide resistance variation. These data add to evidence that nerve insensitivity by mutations in the para-sodium channel gene is a common pyrethroid resistance mechanism in P. xylostella.

Recent electrophysiological experiments have shown that retinal pigment epithelium (RPE) cells begin to produce neuronal-type voltage-dependent sodium currents when placed in dissociated cell culture. In this study, the sodium channel types induced in cultured rat RPE cells were identified. Sodium channel mRNAs encoding two distinct alpha subunits were detected in the cultured RPE cells, brain type II/IIA, and a novel rat mRNA which we have termed RET1. These two sodium channel types may correspond to the TTX-sensitive and TTX-insensitive components of sodium current reported previously in cultured rat RPE cells.

We have examined some of the physiological effects associated with the replacement of extracellular Na+ with Li+ in nominally Ca2+-free saline in the ventral photoreceptors of the horseshoe crab Limulus polyphemus. We observed that replacement of Na+ saline with Li+ saline induced larger voltage-activated inward currents with similar voltage dependence. These currents were absent in Tris+ saline. Anode-break excitation was maintained in Li+ saline but blocked in Tris+ saline. Regenerative events associated with quantum bumps in dark-adapted cells illuminated with dim lights were maintained in Li+ saline. Regenerative events associated with responses to moderately bright illumination were also maintained in Li+ saline. The post-illumination hyperpolarization associated with the Na+/K+-exchange pump (Brown & Lisman, 1972) was present after brief exposure to Li+ saline but disappeared after longer exposure. Following return to Na+ saline, the post-illumination hyperpolarization reappeared. We conclude that (1) Li+ permeates the voltage-dependent Na+ channel, GNa(V), in the photoreceptor plasma membrane; (2) Li+ supports voltage-activated physiological events normally mediated by Na+; and (3) Li+ substitution briefly supports and later inhibits the electrogenic effects of the Na+/K+-exchange pump. The effects of external Li+ on cellular physiology have implications for the interpretation of other studies employing Li+ extracellularly.

Recent advances in the characterisation of insect sodium channel gene sequences have identified a small number of point mutations within the channel protein that are implicated in conferring target-site resistance to pyrethroid insecticides (so-called knockdown resistance or kdr). The L1014F (leucine-to-phenylalanine) mutation located in the centre of segment 6 of the domain II region (IIS6) of the sodium channel (the so-called kdr trait) has been detected in the peach-potato aphid, Myzus persicae (Sulzer), and is considered to be the primary cause of pyrethroid resistance in this species. Here we report on the characterisation of a second mutation, M918T (methione-to-threonine), within the nearby IIS4–S5 intracellular linker (the so-called super-kdr trait) in a field clone also possessing L1014F, with both mutations present in heterozygous form. The resistance phenotype of M. persicae clones possessing various combinations of L1014F and M918T to a wide range of pyrethroids (both Type I and II) was assessed in leaf-dip bioassays and to lambda-cyhalothrin applied at up to ten times the recommended field rate as foliar sprays to aphids feeding on whole plants. Bioassay results demonstrated that presence of both mutations was associated with extreme resistance to all the pyrethroids tested relative to aphids lacking the mutations. Furthermore, this resistance well exceeded that shown by aphids that were homozygous for L1014F but lacking M918T. However, pre-treatment with piperonyl butoxide in the leaf-dip bioassays failed to suppress pyrethroid resistance in aphids carrying one or both of the mutations. The relevance of these findings for monitoring and managing pyrethroid resistance in M. persicae populations in the field is discussed.

Background and objective: Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites.

Methods: Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol.

Results: When depolarizing pulses to 0 mV were started from a holding potential of-70 mV, halfmaximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 µmol for thymol and 376 and 571 µmol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant K d for thymol and menthol from the inactivated state was 22 and 106 µmol for the neuronal and 23 and 97 µmol for the skeletal muscle sodium channel, respectively.

Conclusions: The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.

The voltage-gated ‘glial’ sodium channel NaG belongs to a distinct molecular class within the multi-gene family of mammalian sodium channels. Originally found in central and peripheral glia, NaG has since been detected in neurons in rat dorsal root ganglia (DRG) and may play a role in Schwann cell-axon interactions. We have studied the presence of NaG-like immunoreactivity in the intact and injured human peripheral nervous system using a specific affinity-purified antibody. Nerve fibres in normal and injured peripheral nerves and normal skin exhibited intense NaG-immunoreactivity. Numerous NaG-immunoreactive nerve fibres surrounded neuronal cell bodies within postmortem control DRG, and in DRG avulsed from the spinal cord (i.e. after traumatic central axotomy). There were no significant differences in the pattern of NaG immunostaining between control and avulsed DRG, or with delay after injury. Generally, the neuronal cell bodies were only very weakly immunoreactive to NaG, indicating that the NaG immunoreactivity was predominantly in Schwann cells/myelin. In accord, we demonstrated NaG immunostaining in cultured human and rat Schwann cells, and in distal nerve after wallerian degeneration. NaG thus appears to be a useful new marker for Schwann cells in the human PNS, and a role in neuropathy deserves investigation.

The molecular effects of droperidol (C22H22FN3O2) on single sodium channels from the human brain were investigated using the electrophysiological planar lipid-bilayer technique. Droperidol (0.05–0.8 mm) induced a concentration dependent and voltage independent reduction in the time averaged single channel conductance by two mechanisms: a reduction in the fractional channel open time (major effect, approximately 90%) and a decrease in the channel amplitude (minor effect). The weighted computer fit of the concentration response for the combined effect curve yielded an EC50 of 0.68 mm droperidol and a maximal conductance block of 77%. These blocking effects of droperidol on CNS sodium channels occurred at a concentration range comparable with other specific anaesthetic compounds but far beyond clinical serum levels (up to 0.002 mm). Therefore in contrast with animal preparations (frog peripheral nerve, sodium channel) the human brain sodium channel is not a major target site for droperidol during clinical anaesthesia.