Neuromodulation of Astrocytic K+ Clearance

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

BUFFER ANALYSIS OF THE REACH OF PASSPORT ISSUING SERVICES USING GEOGRAPHIC INFORMATION SYSTEM (GIS) APPLICATIONS (CASE STUDY OF YOUR KUALANAN PASSPORT SERVICE UNIT)

The government organizes public services in the immigration sector in terms of issuing passports through the Directorate General of Immigration which has the responsibility of carrying out immigration functions and determining service standards for each Technical Service Unit owned. In providing public services, the TPI Medan Special Class I Immigration Office is responsible for four districts and two cities covering Langkat Regency, Deli Serdang Regency, Serdang Bedagai Regency, Karo Regency, Medan City and Binjai City. With a large enough working area, it is necessary to establish an Office Work Unit or Passport Service Unit as an effective and efficient way to carry out immigration functions and to bring services closer to the public. The establishment of an Office Work Unit (UKK) and a Passport Service Unit (ULP) based on the workload of the Technical Implementing Unit is very broad so it is necessary to establish an Office Work Unit and Passport Service Unit to optimize immigration functions to the community. The aim is that every community can get the fulfillment of service needs in accordance with the laws and regulations governing the delivery of public services. In the framework of establishing an Office Work Unit (UKK) and Passport Service Unit (ULP), it is necessary to determine a strategic location and can be reached by the community so that it can achieve its maximum function. The Kualanamu Passport Service Unit is located in the Kualanamu Airport area, which is located in Beringin District. Therefore, this study aims to analyze strategic locations in determining the location of ULPs. In order to analyze the location and range of services, a spatial buffering analysis was carried out as well as theories that were considered relevant, such as the theory of Von Thunen, Weber and Christaller. From the spatial analysis process carried out, it can be seen that a strategic location in the formation of ULPs so that the range of services provided can meet the needs of the community.

Neuromodulation of astrocytic K+ clearance

ABSTRACTPotassium homeostasis is a fundamental requirement for normal brain function. Therefore, effective removal of excessive K+ accumulation from the synaptic cleft during neuronal activity is paramount. Astrocytes, one of the most common subtype of glial cells in the brain, play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]°) or impairments of the astrocytic clearance mechanism effect the resonance and oscillatory behaviour of both individual and networks of neurons recorded from C57/BL6 mice of both sexes. These results indicate that astrocytes have the potential to modulate neuronal network activity, however the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behaviour, on the astrocytic clearance process. Our results suggest that some neuromodulators (5-HT; NA) affect astrocytic spatial buffering via gap-junctions, while others (DA; Histamine) affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to recruitment of neurons into ensamble of networks to maximise the synchronous network activity.Significance statementNeuromodulators are known to mediate changes in network oscillatory behaviour and thus impact on brain states. In this study we show that certain neuromodulators directly affect distinct stages of astrocytic K+ clearance, promoting neuronal excitability and network oscillations through parallel activation of both neurons and astrocytes, thus establishing a synergistic mechanism to maximise the synchronous network activity.

Expression of Kir2.1 Inward Rectifying Potassium Channels in Optic Nerve Glia: Evidence for Heteromeric Association with Kir4.1 and Kir5.1

Inward rectifying potassium (Kir) channels comprise a large family with diverse biophysical properties. A predominant feature of central nervous system (CNS) glia is their expression of Kir4.1, which as homomers are weakly rectifying channels, but form strongly rectifying channels as heteromers with Kir2.1. However, the extent of Kir2.1 expression and their association with Kir4.1 in glia throughout the CNS is unclear. We have examined this in astrocytes and oligodendrocytes of the mouse optic nerve, a typical CNS white matter tract. Western blot and immunocytochemistry demonstrates that optic nerve astrocytes and oligodendrocytes express Kir2.1 and that it co-localises with Kir4.1. Co-immunoprecipitation analysis provided further evidence that Kir2.1 associate with Kir4.1 and, moreover, Kir2.1 expression was significantly reduced in optic nerves and brains from Kir4.1 knock-out mice. In addition, optic nerve glia express Kir5.1, which may associate with Kir2.1 to form silent channels. Immunocytochemical and co-immunoprecipitation analyses indicate that Kir2.1 associate with Kir5.1 in optic nerve glia, but not in the brain. The results provide evidence that astrocytes and oligodendrocytes may express heteromeric Kir2.1/Kir4.1 and Kir2.1/Kir5.1 channels, together with homomeric Kir2.1 and Kir4.1 channels. In astrocytes, expression of multiple Kir channels is the biophysical substrate for the uptake and redistribution of K+ released during neuronal electrical activity known as ‘potassium spatial buffering’. Our findings suggest a similar potential role for the diverse Kir channels expressed by oligodendrocytes, which by way of their myelin sheaths are intimately associated with the sites of action potential propagation and axonal K+ release.