The transport and accumulation of K⁺ in higher plant roots is regulated by ABA. Molecular and electrophysiological techniques have identified a number of discrete transporters which are involved in the translocation of K⁺ from the soil solution to the shoots of higher plants. Furthermore, recent reports have shown that ABA regulates K⁺ channel activity in maize and Arabidopsis roots which suggests that ABA regulation of K⁺ transport in roots is, at least in part, ion channel‐mediated. The signalling processes which underlie the ABA regulation of K⁺ channels have been investigated. The effects of ABA on the membrane potential of intact maize root cells were also studied. It was found that ABA regulated the membrane potential of root cells and that this regulation is consistent with the hypothesis that ABA‐induced K⁺ accumulation in roots is mediated by K⁺ channels.

The mechanisms mediating Na⁺ transpdrt in higher plant roots were investigated by applying the patch clamp technique to protoplasts isolated from the cortex and stele of maize roots. In the cortex, permeation of Na+ through a time-dependent K⁺-selective inward rectifier was negligible. Instead, Na⁺ influx into maize roots probably occurs via an instantaneously-activating current. This current was partially inhibited by extracellular Ca²⁺, but was insensitive to extracellular TEA⁺, Cs⁺ and TTX. In outside-out patches, a plasma membrane ion channel was found which mediated an inward Na⁺ current which, at least in part, underlies the whole-cell instantaneously-activating current. The unitary conductance of this channel was 15 pS in 102:121 mM Na⁺ (outsidexytosol). Channel gating was voltage-independent and distinct from that observed for the inwardly rectifying K⁺-selective channel in the same cell type. Increasing extracellular Ca²⁺ from 0.1 to 1 mM reduced the open probability and unitary conductance of this channel. In 102 mM Na⁺ : 123 mM K⁺ (outside:cytosol) a P_Na:P_K of 2.1 was calculated. It is suggested that the plasma membrane Na⁺-permeable channel identified in the cortex of maize roots represents a pathway for low affinity Na⁺ uptake by intact maize roots. In the stele, permeation of Na⁺ through outwardly rectifying K⁺ channels was found to be negligible and the channels are thus unlikely to be involved in the transport of Na⁺ from the root symplasm.

Each year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patentSchistosoma mansonireceived PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers (RandS) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in individual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses (>60 mg/kg) are needed, particularly in smaller children.IMPORTANCESchistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy campaigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda whereSchistosoma mansoniis hyperendemic. Our results demonstrate that a higher dose (>60 mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers.