Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl- ions based on the neuronal Cl- driving force. Established theories regarding the determinants of Cl- driving force have recently been questioned. Here, we present biophysical models of Cl- homeostasis using the pump-leak model. Using numerical and novel analytic solutions, we demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl- driving force. Our models, together with experimental validation, show that while impermeant anions can contribute to setting [Cl-]i in neurons, they have a negligible effect on the driving force for Cl- locally and cell-wide. In contrast, we demonstrate that CCCs are well-suited for modulating Cl- driving force and hence inhibitory signaling in neurons. Our findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.

Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl− ions based on the neuronal Cl− driving force. Established theories regarding the determinants of Cl− driving force have recently been questioned. Here we present biophysical models of Cl− homeostasis using the pump-leak model. Using numerical and novel analytic solutions, we demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl− driving force. Our models, together with experimental validation, show that while impermeant anions can contribute to setting [Cl−]i in neurons, they have a negligible effect on the driving force for Cl− locally and cell-wide. In contrast, we demonstrate that CCCs are well-suited for modulating Cl− driving force and hence inhibitory signalling in neurons. Our findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.

Background Student-run free clinics (SRFCs) combine medical student learning with the provision of free health care. A comprehensive evaluation of patient experience at SRFCs is needed to ensure a balance between valuable clinical experience for students and enhancement of patient care. The aim of this study was to describe patient and medical student perception of care at a longstanding SRFC at the University of Cape Town (UCT). Methods We conducted an observational study at the Students' Health and Welfare Centres Organisation (SHAWCO), a student-run free clinic at UCT. Trained study staff observed clinical encounters between consenting medical students and patients. We surveyed patients on their demographic characteristics, overall satisfaction, and impressions of medical students and physicians at SHAWCO. We surveyed medical students on their level of training, motivation for volunteering, and future career plans. We linked all data from each clinical encounter by a study-generated identification number. Results We surveyed a total of 34 patients and 52 medical students on their experience at SHAWCO. All patients either strongly agreed (88%) or agreed (12%) that they were satisfied with care. Patient satisfaction did not vary with the parameters of care included in multivariable analysis. Patients rated medical students higher than physicians on listening skills, and equally to physicians on all other clinical skills rated. Medical students reported a strong desire to go into primary care and work in underserved settings both before and after volunteering at SHAWCO. Discussion We found a high level of patient satisfaction at SHAWCO, consistent with other studies. Our findings indicate that medical student involvement in care at SRFCs is not a detriment to patient satisfaction.

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