Two Stable Levels of Diastolic Potential at Physiological K+ Concentrations in Human Ventricular Myocardial Cells

• Published in: Circulation research Vol. 66; no. 1; pp. 191 - 201
• Main Authors: McCullough, John R, Chua, William T, Rasmussen, Helge H, Ten Eick, Robert E, Singer, Donald H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.01.1990; Lippincott
• Subjects: Biological and medical sciences; Diastole; Fundamental and applied biological sciences. Psychology; Heart; Heart - physiology; Heart Ventricles - cytology; In Vitro Techniques; Magnesium - pharmacology; Magnesium - physiology; Membrane Potentials; Myocardial Contraction; Myocardium - cytology; Potassium - pharmacology; Potassium - physiology; Strophanthidin - analogs & derivatives; Strophanthidin - pharmacology; Tetrodotoxin - pharmacology; Ventricular Function; Vertebrates: cardiovascular system; Heart; Depolarization; Human; Electrophysiology; Cations; Circulatory system; Ionic current; Permeability; Potassium; Hyperpolarization; Myocyte
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.66.1.191

Cells in many specimens of human ventricle can exhibit either of two stable levels of diastolic potential (DP) when exposed to 4 mM K in vitro (i.e., −78±4 mV or −45±5 mV, mean±SEM). In this report we show that the DP of some partially depolarized human ventricular cells developed a sustained 25–35 mV hyperpolarization (n=28) when bath K concentration (Kb) was raised from 4 to 7 mM. On return of Kb to 4 mM, the DP of most, but not all, of these cells returned to the original depolarized levels. In other cells, the transition between the two levels of DP occurred at variable Kb ranging from 1 to 20 mM. We investigated the ionic mechanism(s) underlying the shifts between the two levels of potential by studying the K dependence of the DP in partially depolarized cells in 22 specimens of human ventricle. DP hyperpolarized an average of 25.6 mV (from −44.4±1.3 to −70.0±1.3 mV; n=25) when Kb was increased from 4 to 7 mM. Intracellular K activity, determined by K-selective microelectrodes, was within the range of normal reported for other mammalian species (106.7±4.4 mM in 4 mM K; n=22) and was unaffected by increasing Kb to 7 mM (111.7±6.6 mM; n=6). Ba (0.05 mM), a blocker of the inward rectifying K current, reversibly prevented the hyperpolarization, whereas acetylstrophanthidin (9 μM) failed to inhibit it. These results suggest that the hyperpolarization was due to a K-dependent increase in K permeability and that electrogenic sodium pumping did not contribute significantly to the process. The ionic basis of the depolarization from a hyperpolarized level of DP also was investigated. Decreasing bath Na concentration and exposure to 30 μM tetrodotoxin did not prevent the depolarization. However, the depolarization could be inhibited by 2 mM Mn. These findings suggest that the depolarization may have been due to a Mn-sensitive inward current.