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Biomedical subjects

P R Adams

Publications and source records attributed to P R Adams.

At least 55 records · Page 3Linked to original sources
PubMed1983

Ca-activated potassium current in vertebrate sympathetic neurons.

Ca-activated K-currents (IC) in sympathetic neurones have been triggered by intracellular Ca-injection or by activating ICa. IC is strongly voltage-dependent, with a peak slope of 11 mV/e-fold depolarization above -50 mV. Relaxation, fluctuation and single channel analysis suggests this to result from voltage-dependent opening and closing rates. Time-constants for channel opening and closing are about 15 msec near zero mV. Single channel conductance is about 100 pS. Currents can be blocked by TEA. IC is activated very rapidly (less than or equal to 5 msec) and sometimes transiently by a depolarizing voltage-step. It is suggested that IC contributes to both spike repolarization and spike after-hyperpolarization. Spontaneous miniature ICs have also been recorded, probably activated by the release of packets of intracellular Ca.

Animals↗
PubMed1983

Substance P inhibits the M-current in bullfrog sympathetic neurones.

Substance P (SP, 2.5-10 microM) was applied by rapid bath perfusion to bullfrog lumbar sympathetic neurones in vitro, voltage-clamped through a single micro-electrode. In unclamped cells, SP produced a depolarization accompanied by an increase in apparent input resistance. Under voltage-clamp a voltage-dependent inward current was induced by SP, during which the time-dependent relaxations induced by square voltage commands were inhibited. It is concluded that SP inhibits the M-current (IM), a species of voltage-dependent K+-current, and that IM-inhibition was the primary cause of the inward current and membrane depolarization in the cells tested.

Animals↗
PubMed1983

Gunshot wound of the aortic arch and esophagus: unusual indication for ascending-to-abdominal aortic bypass graft.

Repair of a gunshot wound of the aortic arch produced severe "coarctation" of the aorta at the origin of the left subclavian artery, requiring the placement of an ascending-to-abdominal aortic bypass graft. This produced an acceptable hemodynamic result, although 10 days later the patient died of infection caused by a concomitant injury of the esophagus. The operative approach for repair of complex injuries of the intrathoracic great vessels can be improved by experience with multiple approaches to elective repair of thoracic vessels.

Journal Article↗
PubMed1982

Voltage-clamp analysis of muscarinic excitation in hippocampal neurons.

Pyramidal cells in the CA1 field of guinea pig hippocampal slices were voltage-clamped using a single microelectrode, at 23-30 degrees C. Small inwardly relaxing currents triggered by step hyperpolarizations from holding potentials of -80 to -40 mV were investigated. Inward relaxations occurring for negative steps between -40 mV and -70 mV resembled M-currents of sympathetic ganglion cells: they were abolished by addition of carbachol, muscarine or bethanechol, as well as by 1 mM barium; the relaxations appeared to invert at around -80 mV; they became faster at more negative potentials; and the inversion potential was shifted positively by raising external K+ concentration. Inward relaxations triggered by steps negative to -80 mV, in contrast, appeared to reflect passage of another current species, which has been labelled IQ. Thus IQ did not invert negative to -80 mV, it was insensitive to muscarinic agonists or to barium, and it was blocked by 0.5-3 mM cesium (which does not block IM). Turn-on of IQ causes the well known droop in the hyperpolarizing electrotonic potential in these cells. The combined effects of IQ and IM make the steady-state current-voltage relation of CA1 cells slightly sigmoidal around rest potential. It is suggested that activation of cholinergic septal inputs to the hippocampus facilitates repetitive firing of pyramidal cells by turning off the M-conductance, without much change in the resting potential of the cell.

Animals↗
PubMed1982

Control of calcium current in rat sympathetic neurons by norepinephrine.

Inward voltage-dependent calcium currents were recorded from clamped rat sympathetic ganglion cells using either one or two microelectrodes. Suppression of potassium current was achieved by applying tetraethylammonium (TEA) externally and TEA plus cesium internally. Peak ICa was observed at 0 mV. ICa was abolished by perfusing cadmium or low calcium medium. ICa was reduced by adding norepinephrine (1-50 micrometers). This effect was not accompanied by any major change in the voltage sensitivity or time course of the residual calcium current. It is suggested that norepinephrine acts by reducing the number of available calcium channels.

Animals↗
PubMed1982

Voltage-sensitive K-currents in sympathetic neurons and their modulation by neurotransmitters.

A description is given of methods for voltage clamping and for studies of the several varieties of K-currents occurring in sympathetic neurons. Conclusions were derived chiefly from experiments conducted on bullfrog lumbar paravertebral sympathetic ganglia but observations made were compared with results obtained from studies of neurons of the rat superior cervical ganglion. Discussion is given of means used for revealing and identifying these currents and for studying actions of drugs, calcium, etc. and circumstances such as membrane state on the four quite distinct time- and voltage-dependent K-currents: IK, IC, IA and IM. The latter (IM) is under direct presynaptic control and the major focus of the paper is on this current and its role. However, considerable information is given concerning the characteristic of the other three (IK, IC and IA).

Animals↗
PubMed1982

M-currents and other potassium currents in bullfrog sympathetic neurones.

1. Bullfrog lumbar sympathetic neurones were voltage-clamped in vitro through twin micro-electrodes. Four different outward (K(+)) currents could be identified: (i) a large sustained voltage-sensitive delayed rectifier current (I(K)) activated at membrane potentials more positive than -25 mV; (ii) a calcium-dependent sustained outward current (I(C)) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (I(A)) activated at membrane potentials more positive than -60 mV after a hyperpolarizing pre-pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K(+) current, the M-current (I(M)).2. I(M) was detected as a non-inactivating current with a threshold at -60 mV. The underlying conductance G(M) showed a sigmoidal activation curve between -60 and -10 mV, with half-activation at -35 mV and a maximal value (G(M)) of 84+/-14 (S.E.M.) nS per neurone. The voltage sensitivity of G(M) could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle.3. I(M) activated and de-activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at approximately 150 ms at -35 mV at 22 degrees C.4. Instantaneous current-voltage (I/V) curves were approximately linear in the presence of I(M), suggesting that the M-channels do not show appreciable rectification. However, the time- and voltage-dependent opening of the M-channels induced considerable rectification in the steady-state I/V curves recorded under both voltage-clamp and current-clamp modes between -60 and -25 mV. Both time- and voltage-dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of I(M).5. It is suggested that I(M) exerts a strong potential-clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation.

Animals↗
PubMed1982

Pharmacological inhibition of the M-current.

1. The effects of muscarinic agonists, luteinizing hormone-releasing hormone (LHRH) analogues, uridine triphosphate (UTP) and divalent cations on K(+)-currents in voltage-clamped bullfrog sympathetic neurones have been studied.2. Muscarine (1-10 muM), D-ala(6) LHRH (1-5 muM), UTP (50-100 muM) and Ba(2+) (1-4 mM) selectively depressed the M-current (I(M)), without appreciable effect on the delayed rectifier, Ca(2+)-activated or transient outward currents (I(K), I(C) or I(A)).3. I(M)-inhibition was characterized by: (a) elimination of slow current relaxations accompanying voltage jumps in the membrane potential range -30 to -60 mV; (b) reduced voltage-dependent chord conductance over this range with no change in the voltage-independent chord conductance at more negative membrane potentials; (c) suppression of outward rectification in the steady-state current-voltage curve between -70 and -25 mV; and (d) development of an inward current which increased in amplitude between -70 and -20 mV in proportion to the decrease in steady-state I(M). The kinetics and voltage sensitivity of residual I(M) were unchanged.4. The magnitude of the inward current produced by muscarine or LHRH could be accounted for quantitatively by the reduction in steady-state I(M). No increase in leak current could be detected in the range -60 to -30 mV. In two cells muscarine (10 muM) increased the leak current and conductance at -70 to -100 mV, but not at more depolarized levels.5. I(M) was not modified by removing extracellular Ca(2+), adding a selective Ca(2+)-channel blocker (Cd(2+)), adding 1 mM-dibutyryl cyclic AMP or 8'Br cyclic GMP, or by intracellular ionophoresis of Ca(2+), 8'Br cyclic GMP, dibutyryl cyclic AMP, GTP-gamma-S or S-adenosylmethionine.6. It is concluded that the principal effects of these agents in unclamped neurones - depolarization, increased input resistance, reduced outward rectification and increased excitability - are due entirely to a selective inhibition of I(M). The intracellular transduction mechanism for I(M) inhibition is unknown.

Action Potentials↗
PubMed1982

Synaptic inhibition of the M-current: slow excitatory post-synaptic potential mechanism in bullfrog sympathetic neurones.

1. Slow muscarinic excitatory post-synaptic currents (slow e.p.s.c.s) generated by preganglionic nerve stimuli were recorded in voltage-clamped bullfrog sympathetic neurones. 2. IM--an outward, voltage-dependent, K+-current--was inhibited during the slow e.p.s.c., and membrane conductance was reduced in a voltage-dependent manner. 3. The slow e.p.s.c. was associated with reduced outward rectification in the steady-state current--voltage (I/V) curve at membrane potentials more positive than--60 m V, with no change in the shape of the non-rectifying part of the I/V curve at more negative potential. 4. The amplitude of the slow e.p.s.c. was reduced by membrane hyperpolarization, to zero at membrane potentials equal to, or more negative than, -60 m V. The voltage sensitivity of the slow e.p.s.c. accorded with that of IM. 5. It is concluded that the slow e.p.s.c. results from a selective inhibition of IM.

Action Potentials↗
PubMed1981

Who do barium ions imitate acetylcholine?

The action of 1-4 mM barium on bullfrog sympathetic ganglion cells was studied using voltage clamp. Barium imitated the action of muscarine, causing depolarization, increased input resistance, tendency to repetitive firing, and a specific inhibition of a slow small outward current termed the M current. Barium did not produce significant short-term inhibition of three other outward currents; the delayed rectifier, the calcium-dependent K current, and the A current.

Acetylcholine↗
PubMed1981

Slow cholinergic and peptidergic transmission in sympathetic ganglia.

Experiments of voltage-clamped bullfrog sympathetic neurons suggest that the "slow depolarization" produced by orthodromic stimulation, by muscarinic agonists, or by the peptide luteinizing hormone-releasing hormone (LHRH), results from the suppression of a time- and voltage-dependent outward K+ current, the "M current" (IM). This current is activated between -60 and -10mV, with a half-maximal activation voltage of -35 mV, a minimum time constant (TM) of 150 ms at -35 mV, and a voltage sensitivity corresponding to a single gating particle with a minimum valency of 4.IM does not show time-dependent inactivation within its activation range and provides the sole potential-sensitive component of the steady outward membrane conductances between -60 and -25 mV. Muscarinic agonists and LHRH selectively depress IM via different receptors, without altering their voltage sensitivity. Although not dependent on external Ca2+ ion, IM is also selectively depressed by Ba2+ ions, so accounting for the cholinomimetic action of Ba2+. It is suggested that IM acts as a braking control on spike discharges and that removal of this control during slow cholinergic and peptidergic transmission provides a unique synaptic tuning mechanism.

Acetylcholine↗
PubMed1981

Voltage clamp analysis of inhibitory synaptic action in crayfish stretch receptor neurons.

Abdominal stretch receptor neurons of Procambarus clarkii were voltage clamped with two microelectrodes, and the synaptic currents set up by stimulating the inhibitory axons, or by rapid bath application of gamma-aminobutyric acid (GABA), were recorded. The inhibitory postsynaptic current (IPSC) decay was exponential, the time constant of decay being increased by membrane depolarization. The IPSC decay was prolonged by diphenylhydantoin, whereas the IPSC amplitude was depressed by picrotoxin. It is suggested that these effects may reflect slowing of the channel closing and opening rates, respectively. Step clamps applied in the presence of GABA yield currents that show inactivation in the 100 ms time range. This inactivation was shown to reflect chloride movement across the membrane. Step clamp data were used to construct dose-response curves. Diphenylhydantoin shifts the dose-response curve to the left with little change in the maximum response. Picrotoxin shifts the curve to the right with a small reduction in the maximum response. These effects are consistent with the postulated effects on channel opening and closing rates, if GABA normally opens a large portion of the channels. Suitable combinations of picrotoxin and diphenylhydantoin acting together leave the dose-response curve unmodified, as predicted.

Animals↗
PubMed1980

Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.

Cholinergic excitation of vertebrate neurones is frequently mediated through the action of acetylcholine on muscarinic (atropine-sensitve) receptors. This type of excitation differs substantially from the better known nicotinic excitation. One difference is that, instead of an increased membrane conductance, a decreased conductance (to K+ ions) frequently accompanies muscarinic depolarisation. This has been detected in sympathetic, cortical and hippocampal neurones. Using voltage-clamped frog sympathetic neurones we have now identified a distinctive voltage-sensitive K+-current, separate from the delayed rectifier current, as the prime target for muscarinic agonists. We have termed this current the M-current, IM.

Animals↗