PubMed Health⌕ Search

Biomedical subjects

J F Storm

Publications and source records attributed to J F Storm.

30 records · Page 2Linked to original sources
PubMed1993

PKA mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons.

The Ca(2+)-activated K+ current IAHP, which underlies spike frequency adaptation in cortical pyramidal cells, can be modulated by multiple transmitters and probably contributes to state control of the forebrain by ascending monoaminergic fibers. Here, we show that the modulation of this current by norepinephrine, serotonin, and histamine is mediated by protein kinase A in hippocampal CA1 neurons. Two specific protein kinase A inhibitors, Rp-cAMPS and Walsh peptide, suppressed the effects of these transmitters on IAHP and spike frequency adaptation. The effects of the cyclic AMP analog 8CPT-cAMP were also inhibited, whereas muscarinic and metabotropic glutamate receptor agonists had full effect. Intracellular application of protein kinase A catalytic subunit or a phosphatase inhibitor mimicked the effects of monoamines or 8CPT-cAMP. These results demonstrate that monoaminergic modulation of neuronal excitability in the mammalian CNS is mediated by protein phosphorylation.

Amino Acid Sequence↗
PubMed1992

2-Amino-3-phosphonopropionate fails to block postsynaptic effects of metabotropic glutamate receptors in rat hippocampal neurones.

Metabotropic glutamate receptors (mGluRs) operate via the phosphoinositide second messenger cascade and have various modulatory effects on central neurones. 2-Amino-3-phosphonopropionate (AP3) has been proposed as a selective antagonist of mGluR and used to explore the physiological functions of mGluR. We have compared the effects of mGluR agonists in the presence and absence of AP3 using intracellular recording from CA1 pyramidal neurones in rat hippocampal slices. Two mM D,L-AP3 or 1 mM L-AP3 did not cause any detectable change in the effects of mGluR agonists trans-1-amino-cyclopentyl-1,3-dicarboxylate (t-ACPD) or quisqualate. These agonists still induced depolarization, inhibition of the slow after-hyperpolarization and slowing of the spike repolarization. The results argue against AP3 being an antagonist of postsynaptic mGluRs.

Action Potentials↗
PubMed1991

Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons.

Activation of metabotropic glutamate receptors (mGluRs, QP or ACPD receptors) has recently been shown to cause depolarization, blockade of the slow after-hyperpolarization and depression of calcium currents in hippocampal pyramidal cells. Here, we report evidence for a new mGluR-mediated effect: slowing of the spike repolarization in CA1 cells in rat hippocampal slices. During blockade of the ionotropic glutamate receptors, the mGluR agonists trans-1-amino-cyclopentyl-1,3-dicarboxylate (t-ACPD), quisqualate or L-glutamate caused spike broadening. In contrast, the ionotropic receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) was ineffective. The spike broadening may act in concert with the other mGluR effects, e.g. by further increasing the influx of Ca2+ ions which, in turn, may contribute to synaptic modulation.

Action Potentials↗
PubMed1990

Potassium currents in hippocampal pyramidal cells.

The hippocampal pyramidal cells provide an example of how multiple potassium (K) currents co-exist and function in central mammalian neurones. The data come from CA1 and CA3 neurones in hippocampal slices, cell cultures and acutely dissociated cells from rats and guinea-pigs. Six voltage- or calcium(Ca)-dependent K currents have so far been described in CA1 pyramidal cells in slices. Four of them (IA, ID, IK, IM) are activated by depolarization alone; the two others (IC, IAHP) are activated by voltage-dependent influx of Ca ions (IC may be both Ca- and voltage-gated). In addition, a transient Ca-dependent K current (ICT) has been described in certain preparations, but it is not yet clear whether it is distinct from IC and IA. (1) IA activates fast (within 10 ms) and inactivates rapidly (time constant typically 15-50 ms) at potentials positive to -60 mV; it probably contributes to early spike-repolarization, it can delay the first spike for about 0.1 s, and may regulate repetitive firing. (2) ID activates within about 20 ms but inactivates slowly (seconds) below the spike threshold (-90 to -60 mV), causing a long delay (0.5-5 s) in the onset of firing. Due to its slow recovery from inactivation (seconds), separate depolarizing inputs can be "integrated". ID probably also participates in spike repolarization. (3) IK activates slowly (time constant, tau, 20-60 ms) in response to depolarizations positive to -40 mV and inactivates (tau about 5s) at -80 to -40 mV; it probably participates in spike repolarization. (4) IM activates slowly (tau about 50 ms) positive to -60 mV and does not inactivate; it tends to attenuate excitatory inputs, it reduces the firing rate during maintained depolarization (adaptation) and contributes to the medium after-hyperpolarization (mAHP); IM is suppressed by acetylcholine (via muscarinic receptors), but may be enhanced by somatostatin. (5) IC is activated by influx of Ca ions during the action potential and is thought to cause the final spike repolarization and the fast AHP (although ICT may be involved). Like IM, it also contributes to the medium AHP and early adaptation. It differs from IAHP by being sensitive to tetraethylammonium (TEA, 1 mM), but insensitive to noradrenaline and muscarine. Large-conductance (BK; about 200 pS) Ca-activated K channels, which may mediate IC, have been recorded. (6) IAHP is slowly activated by Ca-influx during action potentials, causing spike-frequency adaptation and the slow AHP. Thus, IAHP exerts a strong negative feedback control of discharge activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Evaluation of canisters for measuring emissions of volatile organic air pollutants from hazardous waste incineration.

Regulation to control air emissions of toxic organic compounds require the collection and analysis of effluent gas from low level sources such as hazardous waste incinerators. The standard SW-846 Method specifies the use of Tenax and Tenax/charcoal adsorbent traps for collection of volatile organics from incinerators. This study evaluates passivated stainless steel canisters as an alternative to adsorbent traps to eliminate some of the problems associated with adsorbent sampling. Initially the stability of 18 nonpolar, volatile organic compounds was determined in Summa-treated stainless steel canisters with greater than 100 ppmv HCl and saturated with water vapor. All 18 components were stable for a two-week period; however, an interference caused a 10-fold increase in the FID response of trichloroethylene, toluene, and chlorobenzene. No interference of the ECD response was found for any of the 11 compounds detected with the ECD including trichloroethylene. A pilot scale incinerator was sampled using canisters, and the destruction efficiency of 1,1,1-trichloroethane was determined at a concentration of less than 0.5 ppbv while determining 1,1-dichloroethylene, the major product of incomplete combustion, at a concentration of 8000 ppbv from the same sample.

Air Pollutants, Occupational↗
PubMed1989

An after-hyperpolarization of medium duration in rat hippocampal pyramidal cells.

1. In hippocampal pyramidal cells, action potentials are followed by three after-hyperpolarizations (AHPs): a fast AHP (fAHP) lasting 2-5 ms, a medium AHP (mAHP) lasting 50-100 ms, and a slow AHP (sAHP) lasting more than 1 s. The mechanism underlying the mAHP was studied in CA1 cells (n = 46) in rat hippocampal slices, using injection of depolarizing current to elicit discharge. 2. The current underlying the mAHP was studied by single-electrode voltage clamp in two ways. Either the voltage clamp was activated following a burst of spikes, thus recording the early tail current underlying the mAHP (hybrid clamp), or, after blocking the spikes with tetrodotoxin, the early tail current following a depolarizing voltage clamp command (to -20 to -45 mV for 100-400 ms) was measured. In both cases, the early tail current (measured at -60 mV) showed the following characteristics: (a) it decayed exponentially with a time constant of about 50 ms; (b) it was substantially reduced by the muscarinic agonist carbachol (40-50 microM); (c) it was moderately reduced (by 20% or less) by Ca2+-free medium and Ca2+ channel blockers (Cd2+, Mn2+), which abolished the fAHP and the sAHP; (d) it was partly blocked by tetraethylammonium (TEA, 1-10 mM) both before and during Ca2+ channel blockade; (e) it was resistant to noradrenaline (5-10 microM), which blocked the sAHP, and to apamin (100 nM). 3. The mAHP itself, recorded under current clamp, showed properties corresponding to those of the early tail current. 4. Unlike the current underlying the sAHP, which was reduced and reversed by hyperpolarization, the early tail current appeared to be reduced only at potentials down to -80 mV, and to increase at more negative potentials. The early tail current and mAHP-like undershoot at hyperpolarized potentials was blocked by external Cs+, but not by carbachol, in contrast to the early tail current and mAHP at -60 mV. 5. It was concluded that two currents contribute to the mAHP: IM (a voltage-gated muscarine-sensitive K+ current) and IC (a Ca2+-dependent TEA-sensitive K+ current). TEA reduced both the IM (5 mM) and the IC (1 mM) component of the mAHP. When the cell is hyperpolarized, a third current, IQ (a Ca+-sensitive mixed Na+-K+ inward current activated by hyperpolarization), masks the reversal of the mAHP by causing a depolarizing sag which resembles the decay of the mAHP.

Action Potentials↗
PubMed1988

Temporal integration by a slowly inactivating K+ current in hippocampal neurons.

A central aspect of neuronal function is how each nerve cell translated synaptic input into a sequence of action potentials that carry information along the axon, coded as spike frequency. When transduction from a graded depolarizing input to spikes is studied by injecting a depolarizing current, there is often a remarkably long delay to the first action potential, both in mammalian and molluscan neurons. Here, I report that the delayed excitation in rat hippocampal neurons is due to a slowly inactivating potassium current, ID. ID co-exists with other voltage-gated K+ currents, including a fast A current and a slow delayed rectifier current. As ID activates in the subthreshold range, and takes tens of seconds to recover from inactivation, it enables the cell to integrate separate depolarizing inputs over long times. ID also makes the encoding properties of the cell exceedingly sensitive to the prevailing membrane potential.

Action Potentials↗
PubMed1987

Intracellular injection of a Ca2+ chelator inhibits spike repolarization in hippocampal neurons.

The Ca-dependence of spike repolarization and afterhyperpolarizations (AHPs) in Ca1 pyramidal cells, was tested with intracellular electrodes containing the Ca buffers EGTA or 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). EGTA blocked only the slow AHP; but the fast-acting Ca chelator BAPTA also inhibited spike repolarization and the fast AHP. This supports the hypothesis that a fast Ca-activated'K-current contributes to spike repolarization.

Animals↗
PubMed1987

Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

Action Potentials↗
PubMed1987

Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the effect of 4-AP. 5. Pre-pulses or 4-AP broadened the spike less, and in a different manner, than Ca2+-free medium, Cd2+, Co2+, Mn2+, TEA or CTX. The former broadening was uniform, with little effect on the fast a.h.p., whereas the latter affected mostly the last two-thirds of the spike repolarization and abolished the fast a.h.p.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMedDate not supplied

Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning.

A-type K+ channels are known to regulate neuronal firing, but their role in repetitive firing and learning in mammals is not well characterized. To determine the contribution of the auxiliary K+ channel subunit Kvbeta1.1 to A-type K+ currents and to study the physiological role of A-type K+ channels in repetitive firing and learning, we deleted the Kvbeta1.1 gene in mice. The loss of Kvbeta1.1 resulted in a reduced K+ current inactivation in hippocampal CA1 pyramidal neurons. Furthermore, in the mutant neurons, frequency-dependent spike broadening and the slow afterhyperpolarization (sAHP) were reduced. This suggests that Kvbeta1.1-dependent A-type K+ channels contribute to frequency-dependent spike broadening and may regulate the sAHP by controlling Ca2+ influx during action potentials. The Kvbeta1.1-deficient mice showed normal synaptic plasticity but were impaired in the learning of a water maze test and in the social transmission of food preference task, indicating that the Kvbeta1.1 subunit contributes to certain types of learning and memory.

Action Potentials↗