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The Journal of Physiology logoLink to The Journal of Physiology
. 1982;329:485–507. doi: 10.1113/jphysiol.1982.sp014315

Block and activation of the pace-maker channel in calf Purkinje fibres: effects of potassium, caesium and rubidium

Dario DiFrancesco 1
PMCID: PMC1224792  PMID: 6292407

Abstract

1. The effects of low concentrations of Cs+ (0·01-3mM) on the fully activated I-V relation īf(E) for the pace-maker current in calf Purkinje fibres have been investigated. The action of Cs+ is two-fold: in the negative region of the I-V curve Cs+ induces a channel blockade; on the other hand, at more positive potentials Cs+ can produce the opposite effect, i.e. a current increase.

2. Cs+-induced blockade is concentration- and voltage-dependent, as observed on other cation channels. Data in the far negative voltage range (about - 150 to - 50 mV) can be fitted by a simple block model (Woodhull, 1973), which gives a mean value of 0·71 for the fraction of membrane thickness (δ) crossed by Cs+ ions before reaching the blocking site. The value of δ does not appear to be affected by either external Na or external K concentrations. Values for the dissociation constant of the blocking reaction at E = 0 mV (k0) are found in the range 0·5-3·7 mM. In the positive region of the īf(E) relation the current depression caused by channel blockade vanishes. Unexpectedly, in this range the current can be observed to increase with Cs+, and īf(E) curves in different Cs+ concentrations show cross-over.

3. Changing external K+ also produces similar cross-over phenomena. Investigation of this effect reveals that the increase in slope of the I-V curve on raising the external K+ concentration follows Michaelis—Menten kinetics, and can be interpteted in terms of K+-induced channel activation. It is found that 44±6 mM-K+ half-saturates the channel activating reaction.

4. The Cs+-induced current increase is large in low-K+ solutions and vanishes in high-K+ solutions, suggesting a competition between Cs+ and K+ ions in their activating action. Increasing Na+ also limits the Cs+-induced current increase.

5. Rb+ also blocks the if channel, though less efficiently than Cs+. The block caused by Rb+ is, unlike that of Cs+, nearly voltage-independent, and is explained by assuming that the blocking reaction occurs near the external mouth of the channel (mean value of δ is 0·05). The zero-voltage dissociation constant (k0) of the Rb+-blocking reaction ranges between 1·4 and 5·4 mM, and is lower in low-Na+, high-K+ solutions.

6. A possible characterization of the if channel which explains these results includes an inner `blocking' site, to which external Cs+ ions bind, blocking the channel, and a more external `activatory' site, to which K+, Cs+, Rb+ and possibly Na+ ions bind. Binding of K+ to this site induces a current increase either by modulating the channel, or actually by opening the channel itself. A similar mechanism can apply to Cs+ and to Rb+ binding.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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