The neuromodulator adenosine maintains brain homeostasis and regulates complex behaviour via activation of inhibitory and excitatory adenosine receptors (ARs) in a brain region-specific manner. AR antagonists such as caffeine have been shown to ameliorate cognitive impairments in animal disease models but their effects on learning and memory in normal animals are equivocal. An alternative approach to reduce AR activation is to lower the extracellular tone of adenosine, which can be achieved by up-regulating adenosine kinase (ADK), the key enzyme of metabolic adenosine clearance. However, mice that globally over-express an Adk transgene (‘Adk-tg’ mice) were devoid of a caffeine-like pro-cognitive profile; they instead exhibited severe spatial memory deficits. This may be mechanistically linked to cortical/hippocampal N-methyl-D-aspartate receptor (NMDAR) hypofunction because the motor response to acute MK-801 was also potentiated in Adk-tg mice. Here, we evaluated the extent to which the behavioural phenotypes of Adk-tg mice might be modifiable by up-regulating adenosine levels in the cortex/hippocampus. To this end, we investigated mutant ‘fb-Adk-def’ mice in which ADK expression was specifically reduced in the telencephalon leading to a selective increase in cortical/hippocampal adenosine, while the rest of the brain remained as adenosine-deficient as in Adk-tg mice. The fb-Adk-def mice showed an even greater impairment in spatial working memory and a more pronounced motor response to NMDAR blockade than Adk-tg mice. These outcomes suggest that maintenance of cortical/hippocampal adenosine homeostasis is essential for effective spatial memory and deviation in either direction is detrimental with increased expression seemingly more disruptive than decreased expression.

Action potential, which is the foundation of physiology and electrophysiology, is most vital in physiological research. This work starts by detecting cardiac electrophysiology (tachyarrhythmias), combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain, elaborates from generation, induction, initiation, to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism, i.e., connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane. This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias, wounds, denervation supersensitivity, neurogenic pain (hyperalgesia and allodynia), epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years. action potential, spontaneous high-frequency action potential, tachyarrhythmias, atrial fibrillation, wound, denervation supersensitivity, neurogenic pain, hyperalgesia and allodynia, epileptic discharge, diabetic pain, regeneration and development Citation:Shen H Y, Choe W C. Spontaneous high-frequency action potential. Sci China Life Sci, 2011Sci, , 54: 311 -335, doi: 10.1007 Wound, nerve disconnection, and atrial fibrillation (AF) induced by the excessive atrial dilation, are commonly characterized by the spontaneous repetitive discharge. Their common induction is the disconnection of intercellular connection, and their common result is the initiation of spontaneous high-frequency discharge, which discloses the existence of the special action of intercellular connection.The Hodgkin-Huxley model has predicted, and the computer models in applied mathematics have well demonstrated, that potassium leakage causes persistent spontaneous electrifying state with spontaneous oscillation of high-frequency action potential. The sustained disconnection of connecting-end space induces potassium leakage in the connecting-end and consequently the sustained reduction of [K + ] i , which induces in vivo spontaneous high-frequency action potential in plasmalemma.To form an intercellular conduction, connecting-end space exerts action on ion diffusions, the alteration of the space alters ion diffusions (i.e., ionic permeability) in the connecting-end. The abolishment of connecting-end space action causes K + leakage and consequently the reduction of intracellular positive electropotential (IPE) (i.e., the increase of intracellular negative potential), which elevates resting somatic membrane potential and initiates action potential in somatic membrane. SSL action potential is named to the course from the initiation (i.e., connecting-end hyperpolarization) to the termination of somatic membrane action potential.Tachyarrhythmias that are characterized by spontaneous discharge have been most deeply studied. Their inductions contain both mechanical actions and chemical actions, and their courses contain the transformation from traditional action potential to SSL-ty...

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