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.

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.

Inhibition of delayed rectifier K+ currents by copper in acutely dissociated rat hippocampal CA1 neurons

2006 ◽  
Vol 165 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Z NIU ◽  
J CHEN ◽  
S WANG ◽  
M WANG ◽  
X LI ◽  
...  
Keyword(s):  
Delayed Rectifier ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
K Currents

Hydrogen sulfide protects hippocampal CA1 neurons against lead mediated neuronal damage via reduction oxidative stress in male rats

2021 ◽  
Vol 112 ◽  
pp. 101917
Author(s):  
Raheleh Rafaiee ◽  
Hosein Khastar ◽  
Behzad Garmabi ◽  
Malihe Taleb ◽  
Pirasteh Norouzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Neuronal Damage ◽  
Male Rats ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1

Membrane Dysfunction Induced by In Vitro Ischemia in Immature Rat Hippocampal CA1 Neurons

1999 ◽  
Vol 81 (4) ◽  
pp. 1866-1871 ◽  
Author(s):  
T. Isagai ◽  
N. Fujimura ◽  
E. Tanaka ◽  
S. Yamamoto ◽  
H. Higashi
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Input Resistance ◽  
Peak Amplitude ◽  
Immature Rat ◽  
Ca1 Neurons ◽  
In Vitro Ischemia ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1

Membrane dysfunction induced by in vitro ischemia in immature rat hippocampal CA1 neurons. We investigated differences between immature and mature hippocampal neurons in their response to deprivation of oxygen and glucose (in vitro ischemia), using intracellular recording techniques from CA1 pyramidal neurons in rat brain slices. The membrane was more depolarized in immature hippocampal CA1 neurons (postnatal day 7, P7) compared with the adult neurons (P140), and the apparent input resistance in immature neurons was higher than that in adult neurons. In immature neurons, the threshold for action potential generation was high, and the peak amplitude of the action potential was low in comparison with adult neurons. A time-dependent inward rectification, at potentials negative than the resting potential, was prominent in neurons of P14 and P21. After P21, the resting membrane potential, the apparent input resistance, and the threshold and the peak amplitude of the action potential did not significantly change with increasing age. In adult neurons, application of ischemia-simulating medium caused irreversible changes in membrane potential consisting of an initial hyperpolarization followed by a slow depolarization and a rapid depolarization. Once the rapid depolarization occurred, reintroduction of oxygen and glucose failed to restore the membrane potential, a state referred to as irreversible membrane dysfunction. In neurons of ages P7 or P14, the initial hyperpolarization was not apparent, whereas a slow depolarization followed by a rapid depolarization was observed. With development of the neurons, the latency for onset of the rapid depolarization became shorter and its maximal slope increased. Moreover, neurons of ages P14 or P21 showed a partial or complete recovery after reintroduction of oxygen and glucose, unlike mature neurons. In summary, the present study has demonstrated that the initial hyperpolarization and rapid depolarization induced by in vitro ischemia is age dependent. The rapid depolarization is not readily produced in the neurons in age less than P21 during ischemic exposure.

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.

Serotonin agonist and antagonist actions in hippocampal CA1 neurons

1990 ◽  
Vol 68 (5) ◽  
pp. 586-595 ◽  
Author(s):  
Natasha Gurevich ◽  
Peter H. Wu ◽  
Peter L. Carlen
Keyword(s):  
Input Resistance ◽  
Receptor Activation ◽  
Ca1 Neurons ◽  
Binding Characteristics ◽  
Hippocampal Ca1 Neurons ◽  
First Response ◽  
Hippocampal Ca1 ◽  
Agonist And Antagonist ◽  
Mk 212

The actions of serotonin (5-HT) and its putative agonists and antagonists were examined in vitro on hippocampal CA1 neurons using intracellular recordings, demonstrating that the cellular pharmacological effects can not necessarily be predicted from binding characteristics alone. The first response following 5-HT application was often a long-lasting (several minutes) hyperpolarization associated with decreased input resistance. Subsequent 5-HT applications caused only brief hyperpolarizations (30–120 s) and associated decreased input resistance, often followed by membrane depolarization. The post-spike train afterhyperpolarization (AHP) was prolonged for several minutes following the 5-HT induced hyperpolarization. 5-HT1 agonists (8-hydroxy-2-(di-n-propylamino)tetralin, 5-methoxytryptamine, MK-212) caused a prolonged hyperpolarization, decreased input resistance, and enhancement of the AHP. 5-HT applied following agonist application elicited only short-lasting hyperpolarizations. The 5-HT2 antagonists, cyproheptadine and mianserin, and a nonspecific 5-HT antagonist, methysergide, also caused a prolonged hyperpolarization with decreased input resistance. Spiperone, a nonspecific 5-HT antagonist, and ritanserin, a putative specific 5-HT2 receptor antagonist, depolarized CA1 neurons with little or no change in input resistance. The 5-HT-induced short-lasting hyperpolarization was not affected by drop application of 5-HT antagonists, except for methysergide, but perfusion of methysergide, ritanserin, and spiperone attenuated this response. The long-lasting 5-HT hyperpolarization might be mediated by 5-HT1A receptor activation, and the short-lasting hyperpolarization by another serotonergic receptor subtype.Key words: 5-hydroxytryptamine agonists, 5-hydroxytryptamine antagonists, CA1 neurons, intracellular recording, rat hippocampus.

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