Generation of center-surround antagonistic receptive fields in the outer retina occurs via inhibitory feedback modulation of presynaptic voltage-gated calcium channels in cone photoreceptor synaptic terminals. Both conventional and unconventional neurotransmitters, as well as an ephaptic effect, have been proposed, but the intercellular messaging that mediates the inhibitory feedback signal from postsynaptic horizontal cells (HCs) to cones remains unknown. We examined the possibility that proton concentration in the synaptic cleft is regulated by HCs and that it carries the feedback signal to cones. In isolated, dark-adapted goldfish retina, we assessed feedback in the responses of HCs to light and found that strengthened pH buffering reduced both rollback and the depolarization to red light. In zebrafish retinal slices loaded with Fluo-4, depolarization with elevated K ϩ increased Ca signals in the synaptic terminals of cone photoreceptors. Kainic acid, which depolarizes HCs but has no direct effect on cones, depressed the K ϩ -induced Ca signal, whereas CNQX, which hyperpolarizes HCs, increased the Ca signals, suggesting that polarization of HCs alters inhibitory feedback to cones. We found that these feedback signals were blocked by elevated extracellular pH buffering, as well as amiloride and divalent cations. Voltage clamp of isolated HCs revealed an amiloride-sensitive conductance that could mediate modulation of cleft pH dependent on the membrane potential of these postsynaptic cells.

The use of mobile phones has substantially increased throughout the world over the last decade. This has opened up opportunities for the integration of mobile phones as health intervention tools in many aspects of health care, including prevention, diagnosis, data collection, treatment and adherence monitoring and surveillance. Several applications have been explored in human immunodeficiency virus care. The field of tuberculosis (TB) has not exploited the potential of mobile health (m-health) to the same extent, although the opportunities have been recognized. A number of proof-of-concept and pilot studies have been published on m-health in TB care, and an even larger number of studies are available in the grey literature. This article summarizes publications and recent developments at the intersection of TB care and m-health. We show that more rigorous studies evaluating different applications and implementation strategies are needed to establish an evidence base that serves to inform policy and decision making. We outline further areas of research that should be addressed and potential challenges that lie ahead if m-health applications are to enhance the accessibility and quality of TB care.