scholarly journals Protective Effect of a Prosaposin-Derived, 18-Mer Peptide on Slowly Progressive Neuronal Degeneration after Brief Ischemia

2001 ◽  
Vol 21 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Fumio Morita ◽  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Ryuji Hata ◽  
Junzo Desaki ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Avoidance Task ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 Neurons ◽  
Saposin C ◽  
Hippocampal Ca1

Slowly progressive degeneration of the hippocampal CA1 neurons was induced by 3-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident 1 month after ischemia. To investigate the effects of an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained neuronal degeneration, an intracerebroventricular 18MP infusion was initiated 3 days after ischemia. Histopathologic and behavior evaluations were conducted 1 week and 1 month after induction of ischemia. When compared with the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident, as was the number of intact synapses in the hippocampal CA1 region at 1 week and 1 month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons 1 week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1 to 100 fg/mL prevented nitric oxide–induced neuronal damage as expected and significantly up-regulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of 3-minute ischemia is useful in studying the pathogenesis of slowly progressive neuronal degeneration after stroke and in evaluating effects of novel therapeutic agents. It is likely that the 18MP at low extracellular concentrations prevents neuronal apoptosis possibly through up-regulation of the mitochondrial antiapoptotic factor Bcl-xL.

Theta-Frequency Resonance in Hippocampal CA1 Neurons In Vitro Demonstrated by Sinusoidal Current Injection

1998 ◽  
Vol 79 (3) ◽  
pp. 1592-1596 ◽  
Author(s):  
L. Stan Leung ◽  
Hui-Wen Yu
Keyword(s):  
Resonant Frequency ◽  
Hippocampal Neurons ◽  
Ca1 Neurons ◽  
Frequency Resonance ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Theta Frequency ◽  
Sinusoidal Current ◽  
Sinusoidal Currents

Leung, L. Stan and Hui-Wen Yu. Theta-frequency resonance in hippocampal CA1 neurons in vitro demonstrated by sinusoidal current injection. J. Neurophysiol. 79: 1592–1596, 1998. Sinusoidal currents of various frequencies were injected into hippocampal CA1 neurons in vitro, and the membrane potential responses were analyzed by cross power spectral analysis. Sinusoidal currents induced a maximal (resonant) response at a theta frequency (3–10 Hz) in slightly depolarized neurons. As predicted by linear systems theory, the resonant frequency was about the same as the natural (spontaneous) oscillation frequency. However, in some cases, the resonant frequency was higher than the spontaneous oscillation frequency, or resonance was found in the absence of spontaneous oscillations. The sharpness of the resonance ( Q), measured by the peak frequency divided by the half-peak power bandwidth, increased from a mean of 0.44 at rest to 0.83 during a mean depolarization of 6.5 mV. The phase of the driven oscillations changed most rapidly near the resonant frequency, and it shifted about 90° over the half-peak bandwidth of 8.4 Hz. Similar results were found using a sinusoidal function of slowly changing frequency as the input. Sinusoidal currents of peak-to-peak intensity of >100 pA may evoke nonlinear responses characterized by second and higher harmonics. The theta-frequency resonance in hippocampal neurons in vitro suggests that the same voltage-dependent phenomenon may be important in enhancing a theta-frequency response when hippocampal neurons are driven by medial septal or other inputs in vivo.

Na+/Ca2+ exchanger activity induces a slow DC potential after in vitro ischemia in rat hippocampal CA1 region

2000 ◽  
Vol 36 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Hisaaki Uchikado ◽  
Eiichiro Tanaka ◽  
Satoshi Yamamoto ◽  
Takeo Isagai ◽  
Minoru Shigemori ◽  
...  
Keyword(s):  
In Vitro Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Dc Potential

Phencyclidine actions measured intracellularly in hippocampal CA1 neurons

1990 ◽  
Vol 68 (10) ◽  
pp. 1351-1356 ◽  
Author(s):  
Peter W. Kujtan ◽  
Peter L. Carlen
Keyword(s):  
Potassium Conductance ◽  
Input Resistance ◽  
Ca1 Neurons ◽  
Postsynaptic Potentials ◽  
Central Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Potassium Conductances ◽  
Electrophysiological Effects

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 μM – 10 mM), PCP increased the width of action potentials (APs). Doses of 10 μM and higher were associated with decreased action potential amplitude. PCP decreased inhibitory postsynaptic potentials and excitatory postsynaptic potentials but did not alter responses to focally applied GABA. At the lowest dose (0.2 μM), PCP decreased the input resistance (Rin), while at all other doses Rin was increased. PCP decreased post-spike train afterhyperpolarizations at low and medium doses. PCP effects persisted in low calcium medium and also in medium containing 10−6 M tetrodotoxin. It is concluded that in these central neurons, PCP primarily blocks potassium conductances at all doses and, at anesthetic doses, depresses sodium-dependent spikes.Key words: phencyclidine, potassium conductance, CA1 neurons, electrophysiology.

Contribution of ATP-Sensitive Potassium Channels to Hypoxic Hyperpolarization in Rat Hippocampal CA1 Neurons In Vitro

1997 ◽  
Vol 77 (1) ◽  
pp. 378-385 ◽  
Author(s):  
N. Fujimura ◽  
E. Tanaka ◽  
S. Yamamoto ◽  
M. Shigemori ◽  
H. Higashi
Keyword(s):  
Potassium Channels ◽  
Outward Current ◽  
Hypoxic Exposure ◽  
Current Clamp ◽  
Ca1 Neurons ◽  
Intracellular Injection ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Electrode Voltage

Fujimura, N., E. Tanaka, S. Yamamoto, M. Shigemori, and H. Higashi. Contribution of ATP-sensitive potassium channels to hypoxic hyperpolarization in rat hippocampal CA1 neurons in vitro. J. Neurophysiol. 77: 378–385, 1997. To investigate the mechanism of generation of the hypoxia-induced hyperpolarization (hypoxic hyperpolarization) in hippocampal CA1 neurons in rat tissue slices, recordings were made in current-clamp mode and single-electrode voltage-clamp mode. Superfusion with hypoxic medium produced a hyperpolarization and corresponding outward current, which were associated with an increase in membrane conductance. Reoxygenation produced a further hyperpolarization, with corresponding outward current, followed by a recovery to the preexposure level. The amplitude of the posthypoxic hyperpolarization was always greater than that of the hypoxic hyperpolarization. In single-electrode voltage-clamp mode, it was difficult to record reproducible outward currents in response to repeated hypoxic exposure with the use of electrodes with a high tip resistance. The current-clamp technique was therefore chosen to study the pharmacological characteristics of the hypoxic hyperpolarization. In 60–80% of hippocampal CA1 neurons, glibenclamide or tolbutamide (3–100 μM) reduced the amplitude of the hypoxic hyperpolarization in a concentration-dependent manner by up to ∼70%. The glibenclamide or tolbutamide concentrations producing half-maximal inhibition of the hypoxic hyperpolarization were 6 and 12 μM, respectively. The chord conductance of the membrane potential between −80 and −90 mV in the absence of glibenclamide (30 μM) or tolbutamide (100 μM) was 2–3 times greater than that in the presence of glibenclamide or tolbutamide. In contrast, the reversal potential of the hypoxic hyperpolarization was approximately −83 mV in both the absence and presence of tolbutamide or glibenclamide. In ∼40% of CA1 neurons, diazoxide (100 μM) or nicorandil (1 mM) mimicked the hypoxic hyperpolarization and pretreatment of these drugs occluded the hypoxic hyperpolarization. When ATP was injected into the impaled neuron, hypoxic exposure could not produce a hyperpolarization. The intracellular injection of the nonhydrolyzable ATP analogue 5′-adenylylimidodiphosphate lithium salt reduced the amplitude of the hypoxic hyperpolarization. Furthermore, application of dinitrophenol (10 μM) mimicked the hypoxic hyperpolarization, and the dinitrophenol-induced hyperpolarization was inhibited by either pretreatment of tolbutamide or intracellular injection of ATP, indicating that the hypoxic hyperpolarization is highly dependent on intracellular ATP. It is therefore concluded that in the majority of hippocampal CA1 neurons, exposure to hypoxic conditions resulting in a reduction in the intracellular level of ATP leads to activation of ATP-sensitive potassium channels with concomitant hyperpolarization.

scholarly journals Hypoxia with inflammation and reperfusion alters membrane resistance by dynamically regulating voltage-gated potassium channels in hippocampal CA1 neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yoon-Sil Yang ◽  
Joon Ho Choi ◽  
Jong-Cheol Rah
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Input Resistance ◽  
Delayed Rectifier ◽  
Hcn Channels ◽  
Neural Function ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1

AbstractHypoxia typically accompanies acute inflammatory responses in patients and animal models. However, a limited number of studies have examined the effect of hypoxia in combination with inflammation (Hypo-Inf) on neural function. We previously reported that neuronal excitability in hippocampal CA1 neurons decreased during hypoxia and greatly rebounded upon reoxygenation. We attributed this altered excitability mainly to the dynamic regulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and input resistance. However, the molecular mechanisms underlying input resistance changes by Hypo-Inf and reperfusion remained unclear. In the present study, we found that a change in the density of the delayed rectifier potassium current (IDR) can explain the input resistance variability. Furthermore, voltage-dependent inactivation of A-type potassium (IA) channels shifted in the depolarizing direction during Hypo-Inf and reverted to normal upon reperfusion without a significant alteration in the maximum current density. Our results indicate that changes in the input resistance, and consequently excitability, caused by Hypo-Inf and reperfusion are at least partially regulated by the availability and voltage dependence of KV channels. Moreover, these results suggest that selective KV channel modulators can be used as potential neuroprotective drugs to minimize hypoxia- and reperfusion-induced neuronal damage.

Protective actions of various local anesthetics against the membrane dysfunction produced by in vitro ischemia in rat hippocampal CA1 neurons

2004 ◽  
Vol 50 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Aya Yamada ◽  
Eiichiro Tanaka ◽  
Shuhei Niiyama ◽  
Satoshi Yamamoto ◽  
Miho Hamada ◽  
...  
Keyword(s):  
Local Anesthetics ◽  
Ca1 Neurons ◽  
In Vitro Ischemia ◽  
Protective Actions ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1
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