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P R Adams

Publications and source records attributed to P R Adams.

At least 19 recordsLinked to original sources
PubMed1992

Multiple kinetic states underlying macroscopic M-currents in bullfrog sympathetic neurons.

M-current is a time- and voltage-dependent potassium current which is suppressible by muscarinic receptor activation. We have used curve fitting and noise analysis to determine if macroscopic M-currents deviate from a previously predicted simple two-state kinetic scheme. The M-current was best described by three kinetically distinct components: 'fast' (tau 0), 'intermediate' (tau 1) and 'slow' (tau 2) time constants. The 'fast' (tau 0) and 'intermediate' (tau 1) components were identified from the spectra of M-current noise at potentials positive to the cells' resting membrane potential. The 'intermediate' (tau 1) and 'slow' (tau 2) components were seen by curve fitting M-current deactivation currents. The 'intermediate' (tau 1) time constant was voltage dependent (decreasing e-fold in 23 mV), but voltage dependence of the 'fast' (tau 0) and 'slow' (tau 2) components was not obvious. All kinetic components were sensitive to muscarine, with the 'intermediate' (tau 1) and 'slow' (tau 2) being equally so. These data suggest that all components may derive from the same channel population, and that the M-channel may have at least four kinetic states.

Animals↗
PubMed1992

Release of intracellular calcium and modulation of membrane currents by caffeine in bull-frog sympathetic neurones.

1. Calcium release and sequestration were studied in whole-cell voltage-clamped bull-frog sympathetic neurones by image analysis of Fura-2 signals. 2. Application of caffeine (10 mM) to cells voltage clamped at -38 mV caused a rapid increase in intracellular calcium concentration ([Ca2+]i) to a mean value of 352 +/- 33 nM, which activated an outward current. In the continued presence of caffeine the rise in [Ca2+]i slowly declined to a sustained plateau of 196 +/- 20 nM (112 nM above control levels), while the outward current rapidly decayed. Peak calcium release was highest at the edge of the cell. 3. The caffeine-evoked intracellular calcium increase was reduced by two inhibitors of calcium-induced calcium release, ryanodine and procaine. The residual non-suppressible increase in [Ca2+]i may indicate that caffeine can release calcium from two pharmacologically distinct intracellular stores. 4. Inhibition of the caffeine-evoked release of calcium by ryanodine was both concentration and 'use dependent' so that the full inhibitory effect was only observed when caffeine was applied for the second time in the presence of ryanodine. In contrast, the action of procaine did not show any 'use dependence' and unlike ryanodine was fully reversible. 5. The outward current was sensitive to blockers of the large conductance calcium-activated potassium current, Ic. Analysis of variance from this current indicated that it arose at least partly from summation of spontaneous miniature outward currents. 6. The magnitude and duration of calcium release by caffeine was dependent on the resting level of intracellular calcium and the caffeine exposure time. This, together with the pharmacology of the release, suggests that caffeine increases intracellular calcium by sensitizing calcium-induced calcium release. 7. The evoked [Ca2+]i increase was enhanced in amplitude by intracellular application of Ruthenium Red. This effect was mimicked by extracellular application of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) but not by internal application of FCCP or other inhibitors of mitochondrial Ca2+ uptake. This suggests that the evoked increase in [Ca2+]i is predominantly buffered by a Ruthenium Red-sensitive sequestration process which is not mitochondrial.

Animals↗
PubMed1991

Modulation of M-current by intracellular Ca2+.

IM is a voltage- and time-dependent K+ current that is suppressed by muscarinic receptor activation. IM augmentation following agonist washout was blocked by heavily buffering [Ca2+]i using BAPTA. Although IM is not primarily Ca2+ dependent, small increases in [Ca2+]i by photolysis of the "caged" Ca2+ chelator nitr-5 or by evoking action potentials augmented, while larger increases inhibited, IM. Raising [Ca2+]i for prolonged periods, by nitr-5 photolysis, reduced its sensitivity to agonist, leaving a poorly reversible response. These results suggest that IM can be regulated by physiologically relevant changes in [Ca2+]i, placing IM in a unique position to modulate cell excitability.

Animals↗
PubMed1991

Arrest and reversal of atherosclerosis with parenteral nutrition.

In a large subset of patients with atherosclerotic cardiovascular disease, all medical and surgical treatment alternatives have been exhausted or have proved to be ineffective. Intravenous infusion of specially formulated amino acid solutions, developed in the animal laboratory, has been efficacious in arresting and reversing atherosclerosis in humans for the first time. It is anticipated that the principles derived from these precise parenteral studies will eventually permit development of oral and enteral dietary formulations effective for the systemic control and management of atherosclerosis.

Animals↗
PubMed1990

Subcellular calcium transients visualized by confocal microscopy in a voltage-clamped vertebrate neuron.

Confocal laser-scanned microscopy and long-wavelength calcium (Ca2+) indicators were combined to monitor both sustained and rapidly dissipating Ca2+ gradients in voltage-clamped sympathetic neurons isolated from the bullfrog. After a brief activation of voltage-dependent Ca2+ channels, Ca2+ spreads inwardly, and reaches the center of these spherical cells in about 300 milliseconds. Although the Ca2+ redistribution in the bulk of the cytosol could be accounted for with a radial diffusion model, local nonlinearities, suggesting either nonuniform Ca2+ entry or spatial buffering, could be seen. After electrical stimulation, Ca2+ signals in the nucleus were consistently larger and decayed more slowly than those in the cytosol. A similar behavior was observed when release of intracellular Ca2+ was induced by caffeine, suggesting that in both cases large responses originate from Ca2+ release sites near or within the nucleus. These results are consistent with an amplification mechanism involving Ca2(+)-induced Ca2+ release, which could be relevant to activity-dependent, Ca2(+)-regulated nuclear events.

Animals↗
PubMed1990

N-methyl-D-aspartate receptors contribute to excitatory postsynaptic potentials of cat lateral geniculate neurons recorded in thalamic slices.

Neurons of the cat's dorsal lateral geniculate nucleus were recorded intracellularly to study the contribution of N-methyl-D-aspartate (NMDA) receptors to excitatory postsynaptic potentials (EPSPs) and low-threshold calcium spikes. EPSPs were evoked by stimulation of retinogeniculate axons in the optic tract and/or corticogeniculate axons in the optic radiations; EPSPs from both sources were similar. These EPSPs had one or two components, and the second component had several characteristics of NMDA receptor-mediated events. For example, EPSP amplitude decreased when neurons were hyperpolarized and increased when stimulus frequency was increased; these EPSPs could also be blocked reversibly by application of the selective NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). We also studied the influence of NMDA receptors on low-threshold calcium spikes, which are large, voltage- and calcium-dependent depolarizations that are often accompanied by high-frequency action potential discharge. APV blocked synaptically activated low-threshold calcium spikes, but APV had no effect on low-threshold calcium spikes that were elicited by current injection. Therefore, APV does not appear to have a direct effect on the T-type calcium channel that is involved in generation of low-threshold calcium spikes. The voltage and frequency dependence of the NMDA receptor-mediated component of the EPSPs, as well as its ability to trigger low-threshold calcium spikes, provide for complex signal processing in the lateral geniculate nucleus.

2-Amino-5-phosphonovalerate↗
PubMed1989

Bradykinin inhibits a potassium M-like current in rat pheochromocytoma PC12 cells.

We studied the action of bradykinin (BK) on ionic currents in fused pheochromocytoma PC12 cells under voltage-clamp in whole-cell mode, and on intracellular calcium using fura-2 BK induced the development of an outward current associated with an increase in intracellular calcium, followed by inhibition of an M-like current. The outward current was blocked by (+)-tubocurarine, and prevented when the calcium BAPTA or high concentrations of inositol 1,4,5-triphosphate were introduced into the cell, whereas the M-like current and its inhibition by BK remained unaffected. The protein kinase activator phorbol 12,13 dibutyrate partially reduced the M-current. M-current density did not substantially change after prolonged treatment with nerve growth factor.

Animals↗
PubMed1987

Spontaneous miniature outward currents in cultured bullfrog neurons.

Spontaneous miniature hyperpolarizations were observed in cultured bullfrog neurons. Depolarization increased the frequency and amplitude of the events. Under voltage-clamp, these events were manifested as spontaneous miniature outward currents of SMOCs which were usually less than 2 nA, had a rapid rising phase and a slower voltage-dependent exponential decay. Analysis of inter-event intervals suggested that SMOCs occurred randomly, while analysis of their amplitudes yielded exponential amplitude distributions. Mean SMOC amplitudes and SMOC frequency increased with depolarization, even with 100 microM CdCl2 present. Time constants of SMOC decay resembled time constants obtained from voltage-jump experiments on Ca2+-loaded cells, and together with the sensitivity of SMOCs to tetraethyl ammonium (TEA), suggested that SMOCs are due to activation of fast Ca2+-gated potassium channels. We propose that a SMOC occurs when 10-5000 of these channels are activated by punctate intracellular Ca2+ release.

Animals↗
PubMed1987

Effects of phorbol dibutyrate on M currents and M current inhibition in bullfrog sympathetic neurons.

1. Effects of bath-applied phorbol dibutyrate (PDBu) on M currents (IM) and on the inhibition of IM by muscarine and luteinizing hormone-releasing hormone (LHRH) were recorded in voltage-clamped bullfrog lumbar sympathetic ganglion cells. 2. PDBu (0.1-30 microM) produced a slowly developing, irreversible and partial (less than or equal to 60%) inhibition of IM. This effect was not replicated by 4-alpha-phorbol or by vehicle. 3. After treatment with PDBu, residual IM showed a reduced sensitivity to inhibition by muscarine or LHRH but not by Ba2+. The reduced response to muscarine appeared to result from a 10-fold shift in the concentration dependence for inhibition. 4. PDBu did not clearly reproduce the ability of muscarine to inhibit the slow, Ca-activated K current IAHP or to increase the leak conductance at hyperpolarized potentials. The latter effect of muscarine was enhanced, rather than inhibited, by PDBu. 5. IM and IAHP were not inhibited by 1 mM dibutyryl cyclic AMP or by 20 microM forskolin. 6. It is concluded that activation of protein kinase C, but not protein kinase A, partly replicates the effect of muscarine on frog sympathetic neurons.

Animals↗
PubMed1986

Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons.

A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to examine the membrane current responsible for the slow afterhyperpolarization (AHP) in CA1 pyramidal cells. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid clamp). The AHP current showed a dependence on extracellular K+, which was close to that predicted for a K+ current by the Nernst equation. The AHP current could be blocked by Cd2+ or norepinephrine. Although the AHP current showed a requirement for voltage-dependent Ca2+ entry, the current did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential. The effects of norepinephrine, Cd2+, and tetraethylammonium (TEA) were used to identify an AHP current component to the outward current evoked by depolarizing voltage commands from holding potentials that approximate to the resting potential for these cells. The AHP current can contribute significantly to the outward current during the depolarizing command. Upon repolarization it is evident as a slow outward tail current. This slow tail current had the same time constant as AHP currents evoked by hybrid clamp. Fast components to the tail currents were also observed. These were sensitive to Cd2+ and TEA. They probably represent a voltage-sensitive gKCa, sometimes termed C-current. The strong sensitivity to voltage and TEA displayed by the conventionally described gKCa (IC) are properties inconsistent with the AHP. It seems likely that the AHP current (IAHP) represents a Ca2+-activated K+ current separate from IC and that these two currents coexist in the same cell.

Action Potentials↗
PubMed1986

Voltage-dependent currents of vertebrate neurons and their role in membrane excitability.

This chapter reviews what is known of the voltage-dependent conductances of three classes of vertebrate nerve cell, as assessed by somatic voltage clamping. These classes are: (1) bullfrog paravertebral sympathetic ganglion cells; (2) rodent superior cervical sympathetic ganglion cells; and (3) rodent hippocampal pyramidal cells. Of these, bullfrog neurons are the most thoroughly characterized. They possess at least seven distinct voltage-activated conductances. Two of these, called GNa and GCa, carry inward, depolarizing current. They both activate rapidly, and can, under appropriate conditions, generate action potentials. The remaining five conductances are all potassium-mediated, and can thus in principle produce hyperpolarizations or repolarize the action potential. However, because each of these potassium conductances have different sizes, speeds, and voltage thresholds, they play a variety of hyperpolarizing, stabilizing, or braking roles. IC is large, fast, and voltage dependent. Action potentials trigger calcium influx, which rapidly turns on IC. This repolarizes the action potential and turns off IC. However another Ca-dependent current, IAHP, remains active even at negative potentials and leads to a prolonged hyperpolarization. If IC is blocked, spike repolarization slows somewhat, allowing the Hodgkin-Huxley delayed rectifier current IK to develop. This is also large enough to repolarize the spike rapidly, although it is normally preempted by IC. IA and IM are other small potassium currents that activate at more negative potentials than do IC, IK, and IAHP. IA is a transient outward current that mainly influences voltage trajectories following hyperpolarizing current pulses. IM activates progressively during prolonged depolarizing current pulses, and, together with IAHP, explains most of the adaptation seen in these cells. The harmonious counterpoint of this septet of currents explains most of the electrical excitability properties of these cells. However, several of the currents are also synaptically regulated, as a result of transmitters acting on muscarinic or peptide receptors. These slow synaptic actions can lead to dramatic changes in the electrical behavior of the cells. These currents all appear to be present in rat sympathetic ganglion cells also, although detailed analysis here has been hampered by the more complex geometry of these neurons. Furthermore, the roles of the various currents have not been completely defined. It seems possible that IA can contribute to spike repolarization, and clean separation of IC and IAHP has not yet been achieved.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Amylase and growth characteristics of Papulaspora thermophilia.

Mycelial dry weight of Papulaspora thermophilia reached a maximum of about 96 mg after six days of growth in a starch-yeast medium. Extracellular amylase activity was not measurable during this growth period and remained thereafter only about 0.1 unit per ml for 30 days, yet starch concentration reduced rapidly, and reducing sugar appeared in the extracellular medium within the first few days of incubation.

Amylases↗
PubMed1985

Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells.

Healthy bullfrog sympathetic ganglion cells often show a two-component afterhyperpolarization (AHP). Both components can be reduced or abolished by adding Ca-channel blockers or by removing external Ca. Application of a single electrode "hybrid clamp"--i.e., switching from current- to voltage-clamp at the peak of the AHP, reveals that the slow AHP component is generated by a small, slow, monotonically decaying outward current, which we call IAHP. IAHP is blocked by Ca-removal or by apamin and is a pure K current. It is slightly sensitive to muscarine and to tetraethylammonium ion but is much less so than muscarine-sensitive (IM) and fast Ca-dependent (IC) K currents. It also can be recorded in dual-electrode voltage-clamp experiments, where it is seen as a slow, small component of the outward tail current that follows brief depolarizations to 0 mV or beyond. IC is seen as an early, fast, large component of the same tail current. Both components are blocked by Ca removal, but only the IC component is blocked by low doses of tetraethylammonium ion. Thus, bullfrog ganglion cells exhibit two quite distinct Ca-dependent K currents, which differ in size, voltage-sensitivity, kinetics, and pharmacology. These two currents also play quite separate roles in shaping the action potential.

Action Potentials↗
PubMed1979

Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system.

1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed.

Animals↗
PubMed1978

Decamethonium both opens and blocks endplate channels.

Miniature endplate currents, endplate current fluctuations ("membrane noise"), and voltage-jump current relaxations were studied in voltage-clamped frog muscle fibers during decamethonium action. All three types of experiments revealed two kinetic processes controlling the opening of endplate channels, one that reflects agonist action and another that reflects local anesthetic-like blocking activity. The kinetic constants for these two steps were evaluated from measurements of the fast and slow time constants as a function of decamethonium concentration. At -130 mV membrane potential and 13 degrees, the mean open time of decamethonium-activated channels is 2.8 msec. The forward and backward rate constants for channel blocking are 1.7 X 10(7) M-1 sec-1 and 10(3) sec-1. The voltage dependencies of the channel lifetime and of the blocking equilibrium are similar to those seen with pure agonists and local anesthetics, respectively.

Animals↗