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Biomedical subjects

N B Standen

Publications and source records attributed to N B Standen.

At least 91 records · Page 5Linked to original sources
PubMed1981

Calcium current inactivation in identified neurones of Helix aspersa.

1. A two-electrode voltage clamp method was used to study Ca inward currents in identified Helix aspersa neurones bathed in 25 mM-Ca, Na-free saline with TEA and 4-AP. 2. Inward currents were blocked by CdCl2. In Cd delayed outward currents appeared at +30 mV. When two identical depolarizations were separated by a gap inward current turned off to the same level during the two pulses up to +20 mV; above this potential the records cross over. 3. The turn-off of inward current at potentials up to +20 mV was not affected by 0.2 mM-quinine, which reduced outward currents at more depolarized potentials. Inward currents declined exponentially over the first 100 msec with a time constant around 60 msec at 0 mV. Double-pulse experiments gave the same time course of turn-off. 4. When Ca inward current was reduced by lowering [Ca]o or by partial block by Cd the rate and extent of turn-off was reduced. 5. The inactivation curve (obtained using a double pulse with gap method) was U-shaped. The curve was not significantly changed by addition of quinine (0.2 mM) or by changing test pulse size. 6. Recovery of inward currents after a depolarizing prepulse was a double-exponential process, with time constants of 120 msec and 9.4 sec at 10--11 degrees C. 7. Our results are discussed in terms of possible Ca-dependent Ca inactivation and in terms of the possibility of development of an outward Ca-dependent K current.

4-Aminopyridine↗
PubMed1980

The postnatal development of adrenoceptor responses in isolated papillary muscles from rat.

The postnatal development of positive inotropic responses in ventricular tissue was investigated using isolated rat papillary muscles. Responses to exogenous noradrenaline or isoprenaline were already fully developed in preparations from newborn rats. These newborn preparations were also supersensitive to noradrenaline. Responses to field stimulation of intramural nerves or to tyramine were very low in preparations from animals of up to two weeks in age, but had increased to near adult values by 3 weeks of age. This increase in responsiveness was correlated with a progressive increase in sympathetic innervation revealed by fluorescence histochemistry. It is concluded that beta-receptors are present on the ventricular myocardium at birth in the rat, but that positive inotropic responses to sympathetic nerve stimulation do not develop until between 2 and 3 weeks of age.

Aging↗
PubMed1980

Rubidium block and rubidium permeability of the inward rectifier of frog skeletal muscle fibres.

1. A three-electrode voltage clamp method was used to investigate the Rb block of inward rectification in frog sartorius muscle fibres. 2. In a solution containing 80 mM-K+, the potassium conductance increased with increasing hyperpolarization to 3.18 +/- 0.11 mS. cm-2 (n = 17) when (V - VK) was -150 mV. In the presence of Rb+, the conductance increased, fell and increased again with increasing hyperpolarization, i.e. the Rb block was first increased and then reduced by increasing hyperpolarization. Increasing [Rb]o increased the block at all voltages. 3. In a solution containing 80 mM-Rb+ (zero K+) inward currents were recorded when the membrane was hyperpolarized beyond about -60 mV. These currents, which were < 10% the amplitude of those in 80 mM-K solution, were blocked by tetraethylammonium ions. 4. Experiments were carried out in solutions either where both [K]o and [K]i were increased, or where [K]o only was increased. The form of the relation between K conductance and membrane potential appeared to depend on [K]o. The magnitude of the conductance appeared to depend on [K]o and on [K]i. 5. So far as the block by Rb+ is concerned, increasing [K]o appeared to enhance the release of Rb block under large hyperpolarizations. Increasing [K]o and [K]i reduced the Rb block at all membrane potentials. 6. The results of experiments in the presence of Rb+ and Cs+ suggest that these two ions do not compete with each other for a site at which they block inward rectification. Rather, over a range of membrane potentials from -25 to -65 mV, the presence of Cs+ enhances the Rb block and vice versa. 7. Single dissected muscle fibres (from semitendinosus) were used to measure sarcoplasmic resistivity in 80 mM-K solution and 160 mM-K (hyperosmotic) solution. The measured values were 163.2 +/- 11.7 omega x cm and 136.1 +/- 16.0 omega x cm, respectively (n = 7). 8. A semi-empirical model is presented, supposing that Rb interacts with a site in the membrane to produce its blocking effect, but is able to move on through into the sarcoplasm. Internal K+ is supposed to reduce the affinity of the site for Rb+; external K+ is able to enhance the moving on of Rb+ into the sarcoplasm. 9. The implications of our experiments for the nature of the permeability mechanism inward rectification are discussed.

Animals↗
PubMed1979

Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle.

1. A three-electrode voltage clamp method was used to investigate the mechanism of the fall in resting potassium permeability which occurs under extreme hyperpolarization in frog sartorius muscle fibres. 2. Experiments were performed which show that this permeability change is due to a potential dependent block by Na+ ions present in the external solution. 3. Inward K-currents recorded on hyperpolarization turned off exponentially with time. In the presence of Na the steady-state current-voltage relation had a region of negative slope beyond -140 mV. This negative-slope region was removed when Na was replaced by TMA, Tris or Li. Increasing [Na] to 140 mM shifted the negative-slope region to less negative membrane potentials; reducing [Na] to 14 mM shifted the region to more negative potentials. 4. The time constant for the turn-off of the currents (tau) was the same in Na and TMA-containing solutions at membrane potentials positive to -140 mV. At more negative membrane potentials the tau s in Na became progressively shorter than those in TMA. Increasing [Na] to 140 mM (from 70 mM) gave smaller tau s at all potentials. 5. If fibres were hyperpolarized to -240 mV and then repolarized to -160 mV in 70 mM-Na the current recorded during the second pulse turned on with time, often reaching a value greater than that at the end of the first pulse. This behaviour was removed when Na was replaced by TMA or Tris. 6. An estimate of the steady-state relationship between the degree of block and membrane potential was obtained, and could be fitted by an expression for a potential-dependent ionic block with a very low affinity binding site for Na+ in the membrane. 7. The recovery after hyperpolarization of K-currents at the holding potential was examined in two-pulse experiments. In 70 mM-TMA recovery occurred at the same rate whether the initial hyperpolarization was to -120 or to -210 mV. In 70 mM-Na recovery after an initial pulse to -120 mV occurred at the same rate as in TMA, but recovery after a pulse to -210 mV occurred about 9 times faster. These results are consistent with depletion of K from the lumen of the T-system dominating the turn-off of K currents in TMA and in Na for the hyperpolarization to -120 mV, but a different mechanism being involved for the -120 mV pulse in Na. 8. A three-compartment model is presented which attempts to describe the depletion of K from the T-system. The model accurately predicts the time-course for the decline of inward K-currents, both in 10 and 80 mM-K solutions.

Animals↗
PubMed1978

Inward rectification in skeletal muscle: a blocking particle model.

Inwardly rectifying potassium currents were measured in resting frog skeletal muscle in different [K]o. A modle is presneted for inward rectification which supposes that the potassium conductance depends on the K+ concentration within a channel and is reduced by a blocking particle which is driven into the channel by depolarization.

Animals↗
PubMed1978

The postnatal development of adrenoceptor responses to agonists and electrical stimulation in rat isolated atria.

1. Isolated right and left atria from rats of ages ranging from newborn to adult were used to measure chronotropic and inotropic responses to noradrenaline, isoprenaline, tyramine, and electrical stimulation of intramural nerves. 2. Right atria from newborn animals showed increases in rate with noradrenaline, isoprenaline, and tyramine which did not differ significantly from those of atria from adults. The ED50 values for the chronotropic actions of noradrenaline and isoprenaline were not significantly different at any age from the values in adult preparations. 3. Paced left atria from newborn rats showed well developed positive inotropic responses to noradrenaline and isoprenaline. Newborn left atria (and those from 1 and 2 week old animals) were supersensitive to noradrenaline but not to isoprenaline. 4. Left atria from newborn animals showed very small inotropic responses to both tyramine and field stimulation of intramural nerves. These responses developed progressively with age over the first three weeks of life. The results are discussed with respect to the development of cardiac beta-adrenoceptors and of cardiac sympathetic innervation.

Aging↗
PubMed1978

A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions.

1. A three-electrode voltage clamp method was used to investigate the effects of Ba and Sr ions on the inwardly rectifying K conductance of resting frog sartorius muscle fibres. 2. When Ba2+ (0.01-5 mM) was added to the control (115 mM-K+) solution the inward currents recorded during hyperpolarizing voltage steps turned off exponentially with time as the blockade by Ba2+ developed. Outward currents showed no time-dependence. 3. Ba2+ ions reduced both the instantaneous and the steady-state values of currents recorded on hyperpolarization. The blockade was potential-dependent, steady-state currents being increasingly reduced with increasing hyperpolarization. 4. The concentration-effect relation for the blockade of instantaneous currents by Ba2+ could be fitted assuming 1:1 binding of Ba2+ to a receptor, with the block being proportional to the number of Ba2+-filled receptors. The apparent dissociation constant at the holding potential (-5 mV) was 0.65 mM. Concentration-effect relations were shifted along the concentration axis to lower concentrations by hyperpolarization. The apparent dissociation constant was reduced e-fold for a 16.8 mV change in potential. 5. Increasing the [Ba]o increased the rate of onset of the blockade at a given potential. 6. The rate of onset of the blockade had a high temperature dependence (Q10 = 3.15 +/- 0.08). 7. When [K]o was doubled to 230 mM, under conditions where [K]i was also doubled, [Ba]o had to be raised approximately fourfold to produce the same degree and rate of onset of blockade. Similarly, when [K]o was decreased, the degree and rate of onset of blockade were increased for a given [Ba]o. 8. The blockade could be readily removed by removal of Ba2+ from the bathing solution. In addition the blockade which develops on hyperpolarization is removed exponentially on return to the holding potential. 9. The blockade which exists at the holding potential may be removed by a depolarizing prepulse. 10. Sr causes a similar potential-dependent blockade to that by Ba2+, but is around 400 times less effective. 11. The results have been fitted with a model assuming that the permeability mechanism is an aqueous pore with a site which binds one Ba2+ ion or two K+ ions. The site must have affinity for Ba2+ and a low affinity for K+.

Animals↗
PubMed1977

Postnatal development of inotropic responses to nerve stimulation and tyramine in rat atria.

Inotropic responses were measured in isolated rat left atria using an isometric force transducer. In atria from adult rats tyramine administration or field stimulation of intramural cardiac nerves (in the presence of atropine) caused a positive inotropic response which was as great as that obtainable with exogenous noradrenaline. In contrast, atria from newborn animals showed very poor inotropic responses to nerve stimulation or tyramine although they already responded well to noradrenaline. The responses developed progressively with age, reaching adult levels at 3 to 4 weeks of age. It is concluded that the postnatal development of myocardial sympathetic nerves is correlated with a development of the positive inotropic response to sympathetic nerve stimulation or to tyramine.

Animals↗
PubMed1975

Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by calcium influx.

1. Helix aspersa neurones under voltage clamp generate prolonged outward currents (potassium currents) in response to depolarizing command pulses. 2. The potassium currents recorded from cell A were reversibly reduced 25-50% by 10 mM cobalt ions in the bathing medium; 1 mM lanthanum, 10(-6) g/ml. D-600 and 10(-6) g/ml. iproveratril had similar effects but were only partially reversible. 3. The relationship between the potassium currents and the membrane potential had an "n" shape in normal saline. In calcium-free saline (containing 25 mM magnesium) the potassium currents were reduced and the "n" shape was abolished. The effect of calcium-free saline was readily reversible. 4. The voltage-dependence of the calcium-sensitive potassium currents was similar to that of the "late" calcium channel in squid axons (Baker, Hodgkin & Ridgway, 1971). 5. When cell A was depolarents were made up of two exponentially declining components. The slower of the two components was reduced in calcium-free saline. 6. When cell A was depolarized by 150 mV for 10 msec and then repolarized the "tail" currents were made up of a single rapidly declining component. The reversal potential of this component changed by 58 mV for a tenfold change in the external potassium concentration as predicted by the Nernst equation. 7. The reversal potential of "tail" currents having both components was less sensitive to changes in the external potassium concentration. 8. Tetraethylammonium (TEA) ions blocked both calcium dependent and voltage sensitive potassium currents. Each receptor was found to bind a single molecule of TEA. The dissociaton constant was about 10 mM in each case. 9. The intracellular concentration of ionized calcium was estimated from the potential at which there was no apparent calcium influx (the null point). It was between 3 x 10(-8) M and 8 x 10(-8) M with 10(-2) M calcium in the bathing medium. 10. The null point changed 30 mV for a tenfold change in the external calcium concentration as predicted by the Nernst equation. 11. It is concluded that depolarization of Helix neurones activates two typesof potassium channel. One channel is voltage dependent and highly selective for potassium. Activation of the other channel is dependent on the influx (or injection, see Meech, 1972, 1974a) of calcium. This calcium mediated potassium activation system saturates at high external calcium concentrations and is inhibited by external magnesium ions.

Animals↗
PubMed1975

Calcium and sodium ions as charge carriers in the action potential of an identified snail neurone.

1. The soma of cell A in Helix aspersa produced action potentials in sodium-free or calcium-free saline, but not in saline with neither sodium nor calcium. 2. The axon had a sodium-dependent action potential. 3. Tetrodotoxin (5 x 10(-6) M) had no effect on the overshoot except at low external divalent ion concentrations. 4. The action potential in sodium-free saline was blocked by cobalt. 5. The slope of action potential overshoot against sodium concentration in the presence of 10 mM calcium was 10.5 mV/tenfold change. That of overshoot against calcium concentration in the presence of 75 mM sodium was 22 mV/tenfold change. 6. In sodium-free saline the slope of overshoot versus calcium concentration was 27 mV/tenfold change. 7. It is concluded that calcium is an important charge carrier in the action potential of cell A.

Action Potentials↗
PubMed1975

Voltage-clamp studies of the calcium inward current in an identified snail neurone: comparison with the sodium inward current.

1. Membrane currents were recorded under voltage clamp from cell A of the snail Helix aspersa. 2. In sodium-free saline the inward current was reduced to 75% of that in normal saline (containing both sodium and calcium). 3. The inward current in sodium-free saline was dependent on the external calcium concentration. 4. Calcium-free saline reduced the inward current to 30% of that in normal saline. (Na, Ca)-free saline abolished the inward current. 5. Changes in calcium concentration shifted the curve relating calcium conductance to membrane potential along the voltage axis. 6. Inactivation of inward current in both normal saline and sodium-free saline developed exponentially with time. 7. Steady-state inactivation of calcium inward current was similar to that for sodium current and it is concluded that the conductance mechanisms for these two ions bear a close resemblance.

Animals↗