No abstract available.

No abstract available.
Societies, Medical ; Periodicals as Topic ; Organizational Objectives

No abstract available.
Periodicals as Topic ; Publishing ; Veterinary Medicine

No Abstract Available.
Electrophysiology* ; Neuroendocrine Cells*

No abstract available.

The effects of membrane surface charge originated from lipid head groups on ion channels were tested by analyzing the activity of single large conductance Ca2+-activated K+ (maxi K) channel from rat skeletal muscle. The conductances and open-state probability (Po) of single maxi K channels were compared in three types of planar lipid bilayers formed from a neutral phosphatidyledianolamine (PE) or two negatively-charged phospholipids, phosphatidylserine (PS) and phosphatidylinositol (PI). Under symmetrical KCl concentrations (3 apprx 1,000 mM), single channel conductances of maxi K channels in charged membranes were 1.1 apprx 1.7 times larger than those in PE membranes, and the differences were more pronounced at the lower ionic strength. The average slope conductances at 100 mM KCl were 251 +/- 9.9, 360 +/- 8.7 and 356 +/- 12.4 (mean +/- SEM) pS in PE, PS and PI membranes respectively. The potentials at which Po was 1/2, appeared to have shifted left by 40 mV along voltage axis in the membranes formed with PS or PI. Such shift was consistently seen at pCa 5, 4.5, 4 and 3.5. Estimation of the effect of surface charge from these data indicated that maxi K channels sensed the surface potentials at a distance of 8 apprx 9 ANG from the membrane surface. In addition, similar insulation distance (7 apprx 9 ANG) of channel mouth from the bilayer surface charge was predicted by a 3-barrier-2-site model of energy profile for the permeation of K+ ions. In conclusion, despite the differences in structure and fluidity of phospholipids in bilayers, the activities of maxi K channels in two charged membranes composed of PS or PI were strikingly similar and larger than those in bilayers of PE. These results suggest that the enhancement of conductance and Po of maxi channels is mostly due to negative charges in the phospholipid head groups.
Animals ; Axis, Cervical Vertebra ; Head ; Ion Channels ; Ions ; Large-Conductance Calcium-Activated Potassium Channels ; Lipid Bilayers ; Membranes* ; Mouth ; Muscle, Skeletal ; Osmolar Concentration ; Passive Cutaneous Anaphylaxis ; Phosphatidylinositols ; Phospholipids ; Potassium Channels, Calcium-Activated* ; Rats

Voltage-gated K+ (Kv) channels have been considered to be a regulator of membrane potential and neuronal excitability. Recently, accumulated evidence has indicated that several Kv channel subtypes contribute to the control of cell proliferation in various types of cells and are worth noting as potential emerging molecular targets of cancer therapy. In the present study, we investigated the effects of the Kv1.1-specific blocker, dendrotoxin-kappa (DTX-kappa), on tumor formation induced by the human lung adenocarcinoma cell line A549 in a xenograft model. Kv1.1 mRNA and protein was expressed in A549 cells and the blockade of Kv1.1 by DTX-kappa, reduced tumor formation in nude mice. Furthermore, treatment with DTX-kappa significantly increased protein expression of p21Waf1/Cip1, p27Kip1, and p15INK4B and significantly decreased protein expression of cyclin D3 in tumor tissues compared to the control. These results suggest that DTX-kappa has anti-tumor effects in A549 cells through the pathway governing G1-S transition.
Adenocarcinoma/drug therapy/genetics/pathology ; Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Elapid Venoms/*pharmacology ; Elapidae ; Humans ; Kv1.1 Potassium Channel/*antagonists & inhibitors/deficiency/genetics/metabolism ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Potassium Channel Blockers/*pharmacology ; RNA, Messenger/genetics ; Transplantation, Heterologous

BACKGROUND: Cerebral ischemia causes an increase in extracellular potassium ([K+]e) through activation of the KATP channel. This increase in [K+]e could result in neuronal depolarization and a reversal of the glutamate uptake system in glia. This may further contribute to the excessive concentrations of glutamate and asparate in the extracellular space during ischemia. If the early rise in [K+]e during ischemia could be attenuated, less excitotoxic neuronal damage may be the result. However, activation of KATP channels has been shown to attenuate the anoxia induced depolarization in the hippocampus and may reduce the release of excitatory neurotransmitters during cerebral ischemia. In this study, we address the question of whether KATP channel modulation affects [K+]e and whether it is related with extracellular glutamate concentrations. METHODS: After approval by the Animal Care and Use Committee, 18 New Zealand white rabbits were anesthetized with halothane and mechanically ventilated to maintain normocarbia. Microdialysis catheters were inserted into the left dorsal hippocampus and perfused with artificial cerebrospinal fluid at 2 ml/min. K+ sensitive microelectrodes were inserted into the contralateral hippocampus. A pneumatic tourniquet was placed loosely around the neck. Animals were randomized to receive glibenclamide (n=5, KATP blocker, 3.7 mg/kg) or cromakalim (n=5, KATP opener, 0.5 mg/kg). The control group (n=6) had neither drug. Ten-minute period of global cerebral ischemia was produced by inflation of the tourniquet combined with induced hypotension. Hippocampal [K+]e was measured throughout the periischemic period and glutamate concentrations in dialysate were determined by high-performance liquid chromatography. Peak levels were compared by ANOVA. RESULTS: Glutamate concentration significantly increased during ischemia period for all groups (p<0.05). In glibenclamide treated animals, brain glutamate concentration increased markedly during early reperfusion (t=I+15) compared to other groups (p<0.05). There were no statistical differences on ischemia-induced increases in [K+]e among the three groups. CONCLUSIONS: Although it was not possible to demonstrate an effect of modulators of the ATP sensitive K+ channel on [K+]e, glibenclamide increased glutamate during reperfusion. This paradoxical increase in glutamate after administration of a K+ channel blocker suggests that the mechanism of glutamate release is not related to [K+]e change.
Adenosine Triphosphate ; Animals ; Anoxia ; Brain ; Brain Ischemia ; Catheters ; Cerebrospinal Fluid ; Chromatography, Liquid ; Cromakalim ; Extracellular Space ; Glutamic Acid* ; Glyburide ; Halothane ; Hippocampus* ; Hypotension ; Inflation, Economic ; Ischemia* ; KATP Channels ; Microdialysis ; Microelectrodes ; Neck ; Neuroglia ; Neurons ; Neurotransmitter Agents ; Potassium ; Rabbits ; Reperfusion ; Tourniquets