Abstract
We have characterized the inward rectifying background potassium current, iK1, of canine cardiac Purkinje myocytes in terms of its reversal potential, voltage activation curve, and "steady-state" current-voltage relation. The latter parameter was defined from the difference current between holding currents in the presence and absence of 20 mM cesium. Our data suggest that iK1 rectification does not arise exclusively from voltage-dependent gating or exclusively from voltage- dependent blockade by internal magnesium ions. The voltage activation curve constructed from tail currents fit to a Boltzmann two-state model predicts less outward current than is actually observed. The magnesium- dependent rectification due to channel blockade is too fast to account for the time-dependent gating of iK1 that gives rise to the tail currents. We propose a new model of rectification that assumes that magnesium blockade of the channel occurs simultaneously with voltage- dependent gating. The new model incorporates the kinetic schema elaborated by Matsuda, H. (1988. J. Physiol. 397:237-258) to explain the appearance of subconducting states of the iK1 channel in the presence of blocking ions. That schema suggested that iK1 channels were composed of three parallel pores, each of which could be blocked independently. In our model we considered the consequences of partial blockade of the channel. If the channels are partially blocked at potentials where normally they are mostly gated closed, and if the partially blocked channels cannot close, then blockade will have the paradoxical result of enhancing the current carried by iK1.
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biermans G., Vereecke J., Carmeliet E. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes. Pflugers Arch. 1987 Dec;410(6):604–613. doi: 10.1007/BF00581320. [DOI] [PubMed] [Google Scholar]
- Blatter L. A., McGuigan J. A. Free intracellular magnesium concentration in ferret ventricular muscle measured with ion selective micro-electrodes. Q J Exp Physiol. 1986 Jul;71(3):467–473. doi: 10.1113/expphysiol.1986.sp003005. [DOI] [PubMed] [Google Scholar]
- Chang F., Gao J., Tromba C., Cohen I., DiFrancesco D. Acetylcholine reverses effects of beta-agonists on pacemaker current in canine cardiac Purkinje fibers but has no direct action. A difference between primary and secondary pacemakers. Circ Res. 1990 Mar;66(3):633–636. doi: 10.1161/01.res.66.3.633. [DOI] [PubMed] [Google Scholar]
- Cohen I. S., Datyner N. B., Gintant G. A., Mulrine N. K., Pennefather P. Properties of an electrogenic sodium-potassium pump in isolated canine Purkinje myocytes. J Physiol. 1987 Feb;383:251–267. doi: 10.1113/jphysiol.1987.sp016407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen I. S., DiFrancesco D., Mulrine N. K., Pennefather P. Internal and external K+ help gate the inward rectifier. Biophys J. 1989 Jan;55(1):197–202. doi: 10.1016/S0006-3495(89)82792-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiFrancesco D., Ferroni A., Visentin S. Barium-induced blockade of the inward rectifier in calf Purkinje fibres. Pflugers Arch. 1984 Dec;402(4):446–453. doi: 10.1007/BF00583946. [DOI] [PubMed] [Google Scholar]
- Falk R. T., Cohen I. S. Membrane current following activity in canine cardiac Purkinje fibers. J Gen Physiol. 1984 May;83(5):771–799. doi: 10.1085/jgp.83.5.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gadsby D. C. Activation of electrogenic Na+/K+ exchange by extracellular K+ in canine cardiac Purkinje fibers. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4035–4039. doi: 10.1073/pnas.77.7.4035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glitsch H. G., Krahn T., Verdonck F. Activation of the Na pump current by external K and Cs ions in cardioballs from sheep Purkinje fibres. Pflugers Arch. 1989 May;414(1):99–101. doi: 10.1007/BF00585634. [DOI] [PubMed] [Google Scholar]
- Glitsch H. G., Pusch H. On the temperature dependence of the Na pump in sheep Purkinje fibres. Pflugers Arch. 1984 Sep;402(1):109–115. doi: 10.1007/BF00584839. [DOI] [PubMed] [Google Scholar]
- Goldstein D. A. Calculation of the concentrations of free cations and cation-ligand complexes in solutions containing multiple divalent cations and ligands. Biophys J. 1979 May;26(2):235–242. doi: 10.1016/S0006-3495(79)85247-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hess P., Metzger P., Weingart R. Free magnesium in sheep, ferret and frog striated muscle at rest measured with ion-selective micro-electrodes. J Physiol. 1982 Dec;333:173–188. doi: 10.1113/jphysiol.1982.sp014447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hille B. Ionic selectivity, saturation, and block in sodium channels. A four-barrier model. J Gen Physiol. 1975 Nov;66(5):535–560. doi: 10.1085/jgp.66.5.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isenberg G. Cardiac Purkinje fibers: cesium as a tool to block inward rectifying potassium currents. Pflugers Arch. 1976 Sep 30;365(2-3):99–106. doi: 10.1007/BF01067006. [DOI] [PubMed] [Google Scholar]
- Ishihara K., Mitsuiye T., Noma A., Takano M. The Mg2+ block and intrinsic gating underlying inward rectification of the K+ current in guinea-pig cardiac myocytes. J Physiol. 1989 Dec;419:297–320. doi: 10.1113/jphysiol.1989.sp017874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kameyama M., Kakei M., Sato R., Shibasaki T., Matsuda H., Irisawa H. Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature. 1984 May 24;309(5966):354–356. doi: 10.1038/309354a0. [DOI] [PubMed] [Google Scholar]
- Kurachi Y. Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol. 1985 Sep;366:365–385. doi: 10.1113/jphysiol.1985.sp015803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuda H., Matsuura H., Noma A. Triple-barrel structure of inwardly rectifying K+ channels revealed by Cs+ and Rb+ block in guinea-pig heart cells. J Physiol. 1989 Jun;413:139–157. doi: 10.1113/jphysiol.1989.sp017646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuda H. Open-state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea-pig heart cells. J Physiol. 1988 Mar;397:237–258. doi: 10.1113/jphysiol.1988.sp016998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuda H., Saigusa A., Irisawa H. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature. 1987 Jan 8;325(7000):156–159. doi: 10.1038/325156a0. [DOI] [PubMed] [Google Scholar]
- Noma A., Shibasaki T. Membrane current through adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:463–480. doi: 10.1113/jphysiol.1985.sp015722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliva C., Cohen I. S., Mathias R. T. Calculation of time constants for intracellular diffusion in whole cell patch clamp configuration. Biophys J. 1988 Nov;54(5):791–799. doi: 10.1016/S0006-3495(88)83017-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shah A. K., Cohen I. S., Datyner N. B. Background K+ current in isolated canine cardiac Purkinje myocytes. Biophys J. 1987 Oct;52(4):519–525. doi: 10.1016/S0006-3495(87)83241-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheets M. F., Scanley B. E., Hanck D. A., Makielski J. C., Fozzard H. A. Open sodium channel properties of single canine cardiac Purkinje cells. Biophys J. 1987 Jul;52(1):13–22. doi: 10.1016/S0006-3495(87)83183-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soejima M., Noma A. Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch. 1984 Apr;400(4):424–431. doi: 10.1007/BF00587544. [DOI] [PubMed] [Google Scholar]
- Vandenberg C. A. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2560–2564. doi: 10.1073/pnas.84.8.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
