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D DiFrancesco

Publications and source records attributed to D DiFrancesco.

81 records · Page 5Linked to original sources
PubMed1979

The effects of calcium on outward membrane currents in the cardiac Purkinje fibre.

1. Properties of outward membrane currents in Purkinje fibres from sheep's hearts have been studied with particular reference to the effects of external Ca. 2. Altering Cao is found to shift the potential-dependence of channel neutralize negative charges at the external face of the membrane, but the different magnitudes of the effects of low Cao on the pace-maker and plateau currents suggest that the affinities of Ca-binding sites adjacent to each channel type are widely different. 3. Raising Cao causes a positive shift in the pace-maker current reversal potential, EK2, which may reflect a small elevation in the K concentration (Kc) in the restricted cleft space immediately outside the membrane. Other possible causes of the shift in EK2 are also discussed. 4. Raising Cao has effects on the plateau and pace-maker current rectifier relations, and on the time-independent membrane current, which resemble those of a small increase in extracellular K concentration. 5. Possible mechanisms for an increase in Kc in elevated Cao are discussed. Positive shifts in EK2 can be observed even when the membrane current becomes more inward, so it seems unlikely that the increase in Kc results from an activation of K channels by Ca ions. It is possible that increases in Ca partially inhibit the Na:K exchange pump. 6. The maximum transient outward current elicited by strong depolarizing steps is not affected by moderate reductions in Cao. 7. Reducing Nao depresses the pace-maker current rectifier relation with little shift in the activation curve. 8. We conclude that some of the effects of Cao on outward currents are due to shifts in the potential-dependence of channel activation, while others result from a small increase in Kc. No evidence for a direct effect of Ca on K channels has been found in the present study.

Animals↗
PubMed1979

Measurement and significance of the reversal potential for the pace-maker current (iK2) in sheep Purkinje fibres.

1. The apparent reversal potential (Erev) of the pace-maker current (iK2) is found to depend on the experimental protocol used for its measurement. Evidence is presented showing that depolarizing (hyperpolarizing) pulses given before a test hyperpolarization used to determine Erev, shift Erev to more negative (positive) values. These shifts are opposite to those expected if the only effect of pre-pulses were to change the concentration of potassium in extracellular clefts ([K]c) via accumulation and depletion processes. 2. This effect is shown to be due to the fact that Erev is dependent on s0, the degree of activation of iK2 at the start of the test hyperpolarization. 3. When a suitable protocol is used, depletion of cleft K can be demonstrated to take place during a large hyperpolarization. Changes in the level of [K]c induced by pre-pulses must therefore also affect the Erev determination. 4. A simplified three-compartment model has been used to investigate how K accumulation and depletion can affect the time course of iK2, with particular reference to the problem of Erev determination. Computed examples show that the model is able to reproduce the main features of the time course of iK2 recorded near its reversal potential and the changes induced by pre-pulses on Erev measuremnet. By contrast, simulation on a linear cable model rules out the possibility that such results are due to voltage non-uniformity. 5. The three-compartment model predicts that the measured value of Erev differs from EK2 for two reasons: (1) when the recorded current trace is flat iK2 is still outward and decaying, and (2) the K equilibrium potential shifts to more negative values while the test hyperpolarization is applied. 6. The finding that Erev is directly affected by changes in s at the beginning of the test pulse is discussed in relation to the action of agents (such as Ca2+, H+, salicylate, adrenaline and ouabain) which are found to shift both the s00 curve and Erev.

Animals↗
PubMedDate not supplied

Characterization of single pacemaker channels in cardiac sino-atrial node cells.

Normal pacemaking in the mammalian heart is driven by spontaneously active cells located in the sino-atrial (SA) node. The rate of firing of these cells and the modulation of this rate by catecholamines are controlled by if, an inward Na- and K-current that turns on at voltages more negative than -40 mV. The 'pacemaker' current if is also present in other types of cell where its ability to produce and modulate a depolarizing process may be useful. For example, in vertebrate photoreceptors if drives the depolarization that terminates the light-induced hyperpolarization. Currents similar to if are also found in hippocampal neurones and DRG neurones. The present report shows for the first time that the opening of single if-channels of low conductance (1 pS) can be resolved using a modification of the patch-clamp technique on isolated SA-node cells. Modulation of if by adrenaline is shown to be mediated by an increase in the probability of channel opening, whereas the single-channel amplitude remains unchanged.

Animals↗