The higher the concentrations, the slower the channel inactivates. This fact was also confirmed by the structure study of a potassium channel in low salt crystallization conditions, showing a constricted filter conformation. The Nifedipine reason for inactivation has to do with the occupancy of the filter; ions inside the filter stabilize it against collapse. Lowering the ion concentration dilutes the average number of ions in the filter and results in faster inactivation. Thus inactivation is not independent of the opening probability, which could be the reason why we see changes in the inactivation time scale in our experiments, where we modulate the opening probability. In conclusion, we have constructed KvAP-DNA chimeras where the charge on the DNA, which can be manipulated externally by hybridization, pulls electrostatically on the voltage sensing domain, biasing the opening probability of the channel. The resulting gating response is substantially modified, whereas the single channel conductance is unperturbed. It is of course not surprising that one can bias a voltage gated channel through electrostatic interactions, and indeed phosphorylation is used by the cell to that effect. The details are however not simple, for instance, phosphorylation of the Kv channel on giant squid axons has recently been shown to shift the gating behavior, but in the opposite direction to that found here. The present in vitro system may be a well controlled tool to study these effects in detail. For potential applications, this artificially-controlled channel could be delivered to living cells such as neurons possibly through endocytosis of liposomes with reconstituted artificial channels. By designing the addressable sequence of the ssDNA to bind with specific targets, the artificial channels embedded in cells could be made to couple with parts of the regulatory pathways such as micro RNAs or an aptamer-binding protein. An ischemic stroke begins with obstruction of an arterial vessel in the brain, progresses through a cascade of cellular and molecular events, and ultimately leads to cell death. The initial depletion of oxygen leads to a loss of cellular ATP and dysregulation of ion homeostasis at the membrane. The altered ion homeostasis activates voltage-dependent calcium channels and the depolarization of the neuronal membrane can cause massive release of Dimethyl-lithospermate-B neurotransmitters such as glutamate. For glutamatergic neurons, ischemia causes the release of glutamate into the synaptic cleft and extracellular space. The excess glutamate in the extracellular space causes extended activation of ionotropic glutamate receptors. The resulting overstimulation of iGluRs activates intracellular signaling cascades producing excitotoxicity and cell death. The inhibition of glutamate-induced excitotoxicity has been a therapeutic target for the treatment of stroke for many years. For example, acute administration of NMDAR or AMPAR antagonists reduces ischemic damage in rodent models of stroke. Our lab has also previously reported that blocking glutamate release or glutamate-mediated post-synaptic excitability reduces neural degeneration in stroke rats. Taken together, these data support that regulation of glutamate overflow during the ischemic phase can alter outcomes in stroke animals, however, clinical trials based on iGluR antagonists have failed with adverse CNS effects and they possibly impede endogenous neurorepair mechanisms. The release of glutamate occurs within minutes of ischemic onset and therapeutic drugs targeted at blocking excitotoxicity must be administered rapidly or they lose their protective effect. An alternative approach is to augment glutamate clearance from the extracellular space to prevent excitotoxic iGluR stimulation.