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N K Mulrine

Publications and source records attributed to N K Mulrine.

6 recordsLinked to original sources
PubMed1989

Internal and external K+ help gate the inward rectifier.

Recent investigations have demonstrated substantial reductions in internal [K+] in cardiac Purkinje fibers during myocardial ischemia (Dresdner, K.P., R.P. Kline, and A.L. Wit. 1987, Circ. Res. 60: 122-132). We investigated the possible role these changes in internal K+ might play in abnormal electrical activity by studying the effects of both internal and external [K+] on the gating of the inward rectifier iK1 in isolated Purkinje myocytes with the whole-cell patch-clamp technique. Increasing external [K+] had similar effects on the inward rectifier in the Purkinje myocyte as it does in other preparations: increasing peak conductance and shifting the activation curve in parallel with the potassium reversal potential. A reduction in pipette [K+] from 145 to 25 mM, however, had several dramatic previously unreported effects. It decreased the rate of activation of iK1 at a given voltage by several-fold, reversed the voltage dependence of recovery from deactivation, so that the deactivation rate decreased with depolarization, and caused a positive shift in the midpoint of the activation curve of iK1 that was severalfold smaller than the associated shift of reversal potential. These changes suggest an important role of internal K+ in gating iK1 and may contribute to changes in the electrical properties of the myocardium that occur during ischemia.

Animals↗
PubMed1987

Models of the Na-K pump in cardiac muscle predict the wrong intracellular Na+ activity.

The Na-K pump in cardiac Purkinje strands has been carefully studied with voltage clamp and Na+-selective microelectrodes. In three of these studies both the rate of change of intracellular Na+ activity, a(Nai), after pump blockade, and the time constant of reduction of a(Nai) after an Na+ load were measured. These two parameters can be employed with a formalism relating pump activity to a(Nai) in order to predict the a(Nai) in the steady state. Several formalisms were tested: (a) a first-order dependence on a(Nai); (b) a model based on the assumption of a single, saturable, Na+-binding site that must be occupied for transport to occur; (c) a model based on n equivalent, saturable, Na+ binding sites per pump molecule all of which must be occupied for transport to occur. The first two models predicted an a(Nai) that is far below the value of about 6 mM that is experimentally obtained. The third model would work for n greater than or equal to 4. These results suggest that either the cardiac Na-K pump is not well described by available Na-K pump models for n less than 4 or that the measured Na+ influx rate, extrusion rate or a(Nai) are in error.

Animals↗
PubMed1987

Properties of an electrogenic sodium-potassium pump in isolated canine Purkinje myocytes.

1. Purkinje myocytes were isolated from canine Purkinje strands by collagenase exposure and gentle trituration. The myocytes were studied by a switched single-micro-electrode voltage-clamp technique at 37 degrees C in Tyrode solution containing 8 mM-K+ and 2 mM-Ca2+. 2. The dose-response relation for the cardiotonic steroid dihydroouabain (DHO) was obtained by measuring the change in membrane current caused by application of concentrations of 1-100 microM. The KD obtained in fourteen experiments was 3.7 +/- 1.1 microM (mean +/- S.E. of mean). 3. We employed 100 microM-DHO (a concentration more than 25-fold greater than the KD) to estimate the resting pump current (Ip) in the isolated myocytes. A value of 0.27 +/- 0.02 microA microF-1 (mean +/- S.E. of mean, n = 32) was obtained. 4. Myocytes were also exposed to K+-free solution for a period of 200 s. On return to K+-containing Tyrode solution there was a slowly decaying outward current. The time constant of decay of this pump current transient was 87 +/- 8 s (mean +/- S.E. of mean, n = 8). The integral beneath this transient was used to obtain a second estimate of the resting pump current. In four preparations where exposures in DHO and in K+-free solutions were employed the ratio Ip, DHO/Ip, K-free was 1.76 +/- 0.15 (mean +/- S.E. of mean). 5. From the magnitude of resting pump current, in the presence of total pump blockade the Na+ activity should rise at a rate of 1.3 mM min-1. 6. Reducing [K+]o from 8 to 1 mM reduced Ip by more than 40% initially. Ip then slowly increased over the next 30 min. These results suggest that the steady-state inward background current is not greatly altered by changes in [K+]o, and that [Na+]i rises to a new level. The changes in Ip obtained at early times following reduction of [K+]o to 1 or 0.5 mM (t less than 1.75 min) were used to estimate the Km for external K+; a value of 0.8 mM was obtained. 7. The results suggest that the properties of the Na+-K+ pump in isolated canine Purkinje myocytes are similar to those in canine Purkinje strands. This argues against major distortions of measured pump properties in the canine Purkinje strand and for the physiological state of the Na+-K+ pump in the isolated Purkinje myocyte.

Animals↗
PubMed1986

Effects of thallium on membrane currents at diastolic potentials in canine cardiac Purkinje strands.

A two-micro-electrode voltage-clamp technique was used to record membrane currents from canine cardiac Purkinje strands during hyperpolarizing steps to potentials between -70 and -150 mV in Tyrode solutions containing K+ and/or Tl+. Complete replacement of external K+ by equimolar Tl+ increases the instantaneous inwardly rectifying current. The inwardly rectifying region of the instantaneous I-V relation is shifted to more positive potentials and its slope is increased. The diastolic time-dependent current is reduced or reversed. Partial substitution of equimolar Tl+ for K+ reduces the diastolic time-dependent current. The instantaneous I-V relation is shifted inward for molar fractions of Tl+ (YTl) greater than 0.5, and is slightly more inward or unchanged for YTl less than or equal to 0.5. Addition of small amounts of Tl+ shifts the instantaneous I-V relation inward and reduces the diastolic time-dependent current. Addition of Tl+ in solutions containing Ba2+ to block the background inward rectifier has no effect on the instantaneous I-V relation; the diastolic time-dependent (pace-maker) current is reduced. Block of the pace-maker current by Tl+ is largely independent of potential in Ba2+ Tyrode solution. Since Tl+ has opposite effects on the pace-maker current and the inward rectifier, these findings support other evidence that the pace-maker current is not part of the background inward rectifier.

Action Potentials↗
PubMed1983

Actions of barium and rubidium on membrane currents in canine Purkinje fibres.

The actions of Ba2+ and Rb+, two blockers of background K+ conductance, were investigated. Recent studies performed on ungulate Purkinje fibres have suggested that the pace-maker current is an inward current activated by hyperpolarization. This hypothesis is based on the assumption that Ba2+ reduces the inwardly rectifying background K+ conductance without affecting the pace-maker current. Addition of 5 mM-BaCl2 to the bathing Tyrode solution decreases background K+ permeability and eliminates the reversal of the pace-maker current. The reversal reappears on return to Ba2+-free Tyrode solution. 5 mM-BaCl2 also reduces the time-dependent current at pace-maker potentials positive to about -95 mV in 4 mM-K+ Tyrode solution. The pace-maker current in Ba2+ Tyrode solution usually does not have an exponential time course, and often decays non-monotonically. It can take more than two minutes to reach a steady state. The fast initial component of membrane current, which is observed on hyperpolarizing in the pace-maker potential range in Purkinje fibres and which has been called the 'depletion current', is still present in Ba2+ Tyrode solution, but is reduced or eliminated if 10 mM-CsCl is added to the Ba2+ Tyrode solution. The addition of Cs+ is accompanied by an outward shift in membrane current in Ba2+ Tyrode solution. Ba2+ reduces the background K+ permeability in a dose-dependent manner. Addition of between 0.5 and 1 mM-BaCl2 achieves a maximum effect. Raising the amount of BaCl2 above this level reduces the time-dependent current even when no further effect on background permeability is observed. Rb+ substitution for K+ reduces the magnitude of the pace-maker current at potentials positive to -100 mV, eliminates the reversal of the pace-maker current, shifts the activation range to more negative potentials, and decreases the voltage dependence of pace-maker current kinetics. Rb+ addition to Tyrode solution has little effect on pace-maker current magnitude or time course positive to -90 mV, but does shift the reversal to more negative potentials. The available evidence suggests that the pace-maker current in Ba2+ Tyrode solution is an inward current activated by hyperpolarization. However, Ba2+ blocks an unknown fraction of the pace-maker current in a dose-dependent, and possibly voltage-dependent manner. Also, the presence of a slow component of pace-maker decay suggests that the standard Hodgkin-Huxley formalism for the analysis of pace-maker currents is inappropriate.

Action Potentials↗