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M W Veldkamp

Publications and source records attributed to M W Veldkamp.

22 records · Page 2Linked to original sources
PubMed1994

Effects of intracellular sodium and hydrogen ion on the sodium activated potassium channel in isolated patches from guinea pig ventricular myocytes.

OBJECTIVE: The Na+ activated K+ channel (IK(Na)) may be activated during ischaemia when the intracellular Na+ concentration is raised. As ischaemia is also associated with intracellular acidification, the influence of intracellular pH on this K+ channel was investigated. METHODS: The effects of intracellular Na+ and H+ on the IK(Na) channel were investigated in isolated patches from guinea pig ventricular myocytes by the patch clamp technique. RESULTS: Increase of intracellular Na+ increased the open probability of the channel. Intracellular acidification had no effect on the single channel conductance, but significantly decreased the open probability of the channel in the pH range 7.5-6.5. The effect of intracellular pH on open probability was about the same in a wide range of intracellular Na+ concentrations. The lower open probability induced by acidification seemed to be caused by prolonged closed times. CONCLUSIONS: Because the effects of increased intracellular Na+ and decreased pH on open probability are opposite, it is suggested that the IK(Na) channel might be important under conditions of raised intracellular Na+ with relatively unchanged intracellular pH. Consequently, it is hypothesised that this channel may be involved in adaptation of action potential duration at high heart rate and in action potential shortening in the border zone of regional ischaemic areas.

Action Potentials↗
PubMed1993

Single delayed rectifier channels in the membrane of rabbit ventricular myocytes.

In rabbit ventricular cells, the delayed rectifier current (IK) has not been extensively studied, and properties of single IK channels still need to be determined. In this study, we present data on a voltage-dependent channel in rabbit ventricular cells; the properties indicate that it is an IK channel. Patch-clamp experiments were carried out on cell-attached and inside-out patches of rabbit ventricular cells. Single-channel currents were recorded at negative potentials as inward currents with 150 mM K+ in the pipette. Voltage-dependent channel activity was only present after the return from a depolarizing test pulse, indicating activation on depolarization. Single-channel conductance calculated from the current-voltage relation was 13.1 pS (pooled data, n = 8). The shift in reversal potential of the unitary currents, determined at 150 and 300 mM K+ at the intracellular side of the membrane, showed that the channels were highly permeable to potassium ions. Increase of the duration or the amplitude of the depolarizing test pulse increased channel activity. The time constant for activation at +30 mV was 187 msec (pooled data, n = 4). Half-activation potential was -4.9 +/- 3.8 mV (mean +/- SD), and the slope factor was 7.2 +/- 3.7 mV (mean +/- SD). Current tails, reconstructed from averaged single-channel currents, revealed that the time course of deactivation decreased from 694 +/- 73 msec at -80 mV to 136 +/- 39 msec at -110 mV. Additional evidence that the channel was indeed an IK channel was provided by the observation that the channel was blocked by 10(-7) M E-4031, a class III antiarrhythmic agent that has been shown to block a component of the macroscopic IK in guinea pig heart.

Action Potentials↗
PubMedDate not supplied

A single Na(+) channel mutation causing both long-QT and Brugada syndromes.

Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT(3)) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members. ECGs were obtained from 79 adults with a defined genetic status (carriers, n=43; noncarriers, n=36). In affected individuals, PR and QRS durations and QT intervals are prolonged (P<0.0001 for all parameters). ST segment elevation in the right precordial leads is present as well (P<0.0001). Twenty-five family members died suddenly, 16 of them during the night. Expression of wild-type and mutant Na(+) channels in Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV negative shift of the steady-state inactivation curve and an 8.1-mV positive shift of the steady-state activation curve. The functional consequence of both shifts is likely to be a reduced Na(+) current during the upstroke of the action potential. LQT(3) and Brugada syndrome are allelic disorders but may also share a common genotype.

Adult↗