Mediation by Intracellular Calcium-Dependent Signals of Hypoxic Hyperpolarization in Rat Hippocampal CA1 Neurons In Vitro

1997 ◽  
Vol 77 (1) ◽  
pp. 386-392 ◽  
Author(s):  
S. Yamamoto ◽  
E. Tanaka ◽  
H. Higashi
Keyword(s):  
Intracellular Calcium ◽  
Reversal Potential ◽  
Ca1 Neurons ◽  
Calcium Dependent ◽  
Calmodulin Inhibitor ◽  
Hippocampal Ca1 Neurons ◽  
Calmodulin Kinase ◽  
Hippocampal Ca1 ◽  
Intracellular Ca

Yamamoto, S., E. Tanaka and H. Higashi. Mediation by intracellular calcium-dependent signals of hypoxic hyperpolarization in rat hippocampal CA1 neurons in vitro. J. Neurophysiol. 77: 386–392, 1997. In response to oxygen deprivation, CA1 pyramidal neurons show a hyperpolarization (hypoxic hyperpolarization), which is associated with a reduction in neuronal input resistance. The role of extra- and intracellular Ca2+ ions in hypoxic hyperpolarization was investigated. The hypoxic hyperpolarization was significantly depressed by tolbutamide (100 μM); moreover, the response was reversed in its polarity in medium containing tolbutamide (100 μM), low Ca2+ (0.25 mM), and Co2+ (2 mM), suggesting that the hypoxic hyperpolarization is mediated by activation of both ATP-sensitive K+ (KATP) channels and Ca2+-dependent K+ channels. The hypoxic depolarization in medium containing tolbutamide, low Ca2+, and Co2+ is probably due to inhibition of the electrogenic Na+-K+ pump and concomitant accumulation of interstitial K+. Hypoxic hyperpolarizations were depressed in either low Ca2+ (0.25 or 1.25 mM) or high Ca2+ (5 or 7.5 mM) medium (control: 2.5 mM), indicating that there is an optimal extracellular Ca2+ concentration required to producethe hypoxic hyperpolarization. Bis-( o-aminophenoxy)- N,N,N′,N′tetraacetic acid (BAPTA)-AM (50–100 μM), procaine (300 μM), or ryanodine (10 μM) significantly depressed the hypoxic hyperpolarization, suggesting that Ca2+ released from intracellular Ca2+ stores may have an important role in the generation of hypoxic hyperpolarization. The high-affinity calmodulin inhibitor N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonomide hydrochloride (W-7) (5 μM) completely blocked, whereas the low-affinity calmodulin inhibitor N-(6-aminohexyl)-1-naphthalenesulfonomide hydrochloride (W-5) (50 μM) did not affect, the hypoxic hyperpolarization. The calmodulin inhibitor trifluoperazine (50 μM) also suppressed the hypoxic hyperpolarization. In addition, calcium/calmodulin kinase II inhibitor 1-[N,O-bis(1,5-isoquinol-inesulfonyl)- N-methyl-l-tyrosyl]-4-phenyl-piperazine (KN-62) (10 μM) markedly depressed the amplitude and net outward current of the hypoxic hyperpolarization without affecting the reversal potential. In contrast, neither the myosin light chain kinase inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexa-hydro-1,4-diazepin hydrochloride (ML-7) (10 μM) nor the protein kinase A inhibitorN-[2-(p-bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide(H-89) (1 μM) significantly altered the hypoxic hyperpolarization. These results suggest that calmodulin kinase II, which is activated by calmodulin, may contribute to the generation of the hypoxic hyperpolarization. In conclusion, the present study indicates that, in the majority of hippocampal CA1 neurons, the hypoxic hyperpolarization is due to activation of both KATP channels and Ca2+-dependent K+ channels.

Mechanisms Underlying the Rapid Depolarization Produced by Deprivation of Oxygen and Glucose in Rat Hippocampal CA1 Neurons In Vitro

1997 ◽  
Vol 78 (2) ◽  
pp. 891-902 ◽  
Author(s):  
E. Tanaka ◽  
S. Yamamoto ◽  
Y. Kudo ◽  
S. Mihara ◽  
H. Higashi
Keyword(s):  
Membrane Potential ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Tissue Slices ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Basal Dendrites ◽  
Hippocampal Ca1 ◽  
Rat Tissue

Tanaka, E., S. Yamamoto, Y. Kudo, S. Mihara, and H. Higashi. Mechanisms underlying the rapid depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro. J. Neurophysiol. 78: 891–902, 1997. Intracellular recordings were made to investigate the mechanism, site, and ionic basis of generation of the rapid depolarization induced by superfusion with ischemia-simulating medium in hippocampal CA1 pyramidal neurons of rat tissue slices. Superfusion with ischemia-simulating medium produced a rapid depolarization after ∼6 min of exposure. When oxygen and glucose were reintroduced, the membrane potential did not repolarize but depolarized further, reaching 0 mV ∼5 min after reintroduction. Simultaneous recordings of changes in cytoplasmic Ca2+ concentration ([Ca2+]i) and membrane potential recorded from 1-[6-amino-2-(5-carboxy-2-oxazolyl)-5-benzofuranyloxy] - 2 - ( 2 - amino - 5 - methylphenoxy ) - ethane - N, N, N′ , N′tetraacetic acid pentaacetoxymethyl ester (Fura-2/AM) loaded slices revealed a rapid increase in [Ca2+]i in all CA1 layers corresponding to the rapid depolarization of the soma membrane. The result suggests that the rapid depolarization is generated not only in the soma but also in the apical and basal dendrites. Application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), dl-2-amino-4-phosphonobutyric acid, and dl-2-amino-3-phosphonopropionic acid or bicuculline did not affect the amplitude and the maximal slope. Reduction in the concentration of extracellular Ca2+ or addition of CNQX or dl-2-amino-5-phosphonopentanoic acid delayed the onset of the rapid depolarization. The amplitude of the rapid depolarization recorded with Cs acetate electrodes in tetraethylammonium-containing medium had a linear relationship to the membrane potential between −50 and 20 mV. The reversal potential was shifted in the hyperpolarizing direction by a decrease in either [Na+]o or [Ca2+]o, whereas the reversal potential was shifted in the depolarizing direction by a decrease in [Cl−]o or using CsCl electrodes. An increase or decrease in [K+]o did not affect the reversal potential. These results indicate that the rapid depolarization is Na+, Ca2+, and Cl− dependent. The lack of effects of changes in [K+]o is probably due to the accumulation of interstitial K+ before generating the rapid depolarization. Prolonged application of ouabain (30 μM) caused an initial small hyperpolarization, a subsequent slow depolarization, and a rapid depolarization. In summary, the present study has demonstrated that the rapid depolarization is voltage-independent and is probably due to a nonselective increase in permeability to all participating ions, which may occur only in pathological conditions. The underlying conductance change is primarily the result of inhibition of Na,K-ATPase activity in the recorded neuron.

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.

Mechanisms of Potentiation by Calcium-Calmodulin Kinase II of Postsynaptic Sensitivity in Rat Hippocampal CA1 Neurons

1997 ◽  
Vol 78 (5) ◽  
pp. 2682-2692 ◽  
Author(s):  
Aneil M. Shirke ◽  
Roberto Malinow
Keyword(s):  
Time Course ◽  
Long Term Potentiation ◽  
Similar Process ◽  
Fluctuation Analysis ◽  
Maximal Effect ◽  
Internal Perfusion ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Calmodulin Kinase ◽  
Hippocampal Ca1

Shirke, Aneil M. and Roberto Malinow. Mechanisms of potentiation by calcium-calmodulin kinase II of postsynaptic sensitivity in rat hippocampal CA1 neurons. J. Neurophysiol. 78: 2682–2692, 1997. Preactivated recombinant α-calcium–calmodulin dependent multifunctional protein kinase II (CaMKII*) was perfused internally into CA1 hippocampal slice neurons to test the effect on synaptic transmission and responses to exogenous application of glutamate analogues. After measurement of baseline transmission, internal perfusion of CaMKII* increased synaptic strength in rat hippocampal neurons and diminished the fraction of synaptic failures. After measurement of baseline responses to applied transmitter, CaMKII* perfusion potentiated responses to kainate but not responses to N-methyl-d-aspartate. Internal perfusion of CaMKII*potentiated the maximal effect of kainate. Potentiation byCaMKII* did not change the time course of responses to kainate, whereas increasing response size by pharmacologically manipulating desensitization or deactivation rate constants significantly altered the time course of responses. Nonstationary fluctuation analysis of responses to kainate showed a decrease in the coefficient of variation after potentiation by CaMKII*. These data support the hypothesis that CaMKII increases postsynaptic responsiveness by increasing the available number of active α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate channels and suggests that a similar process may occur during the expression of long-term potentiation.

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.

scholarly journals Calcium Movement in Ischemia-Tolerant Hippocampal CA1 Neurons after Transient Forebrain Ischemia in Gerbils

1996 ◽  
Vol 16 (5) ◽  
pp. 915-922 ◽  
Author(s):  
Shinsuke Ohta ◽  
Shigeru Furuta ◽  
Ichiro Matsubara ◽  
Keiji Kohno ◽  
Yoshiaki Kumon ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neuronal Death ◽  
Pyramidal Neurons ◽  
Forebrain Ischemia ◽  
Electron Microscopic ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Before And After ◽  
Intracellular Ca

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracelluar Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca2+-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca2+-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca2+-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequestration and plasma membrane Ca2+-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.

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.

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
Sign in / Sign up

Export Citation Format

Share Document