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Review
. 2017 Mar;10(3):e004667.
doi: 10.1161/CIRCEP.116.004667.

Electrophysiology of Hypokalemia and Hyperkalemia

James N Weiss  1 , Zhilin Qu  2 , Kalyanam Shivkumar  2
Affiliations
Review

Electrophysiology of Hypokalemia and Hyperkalemia

James N Weiss et al. Circ Arrhythm Electrophysiol. 2017 Mar.
No abstract available

Keywords: hyperkalemia; hypokalemia; ischemia; potassium channels; sodium.

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Figures

Figure 1
Figure 1
A. Interconnectedness of K+, Na+ and Ca2+ balances in the cardiac myocyte. Outward K+ loss through K+ channels (left) is recovered by the Na+-K+ ATPase removing 3 Na+ ions in exchange for 2 K+ ions. Some Na+ ions enter the cell via Na+ channels, but most via Na+-Ca2+ exchange (NCX) during diastole, which exchanges 1 Ca2+ ion for 3 Na+ ions. In the steady state, the Ca2+ removed by NCX balances the Ca2+ entering the cell via Ca2+ channels. Most Ca2+ in the cell recycles between the sarcoplasmic reticulum (SR) and cytoplasm, with uptake by sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) and release through ryanodine receptors (RyR). Cytoplasmic free Ca2+ activates CaMK, which regulates the properties of Na+, Ca2+ and K+ channels, and RyR in the SR (dotted arrows). B. Effects of hypokalemia on the AP. Superimposed AP recordings from an isolated rabbit ventricular myocyte with [K+]o=5.4 mmol/l (black trace) versus [K+]o= 2.7 mmol/l (red trace), showing hyperpolarized Em and EADs, the latter suppressed by the CaMK blocker KN-93 (green trace), but not by inactive KN-92 (blue trace). Modified from Pezhouman et al with permission.
Figure 2
Figure 2
[K+]o dependence of hypokalemia-induced VT/VF in isolated rabbit hearts, without or with dofetilide. When [K+]o was lowered, the incidence of VT/VF within 90 minutes progressively increased to 100% at 2.0 and 1.0 mmol/l (black circles). Dofetilide (1 μmol/l) shifted the dose-response curve to the right. Reproduced with permission from Pezhouman et al.
Figure 3
Figure 3
Regional chaos synchronization of EADs in tissue. In simulated paced homogeneous cardiac tissue, electrotonic coupling causes regional chaos synchronization to generate EAD islands (red regions), separated by regions without EADs (blue), whose position and size vary from beat-to-beat. Beat #1 illustrates a scenario in which a triggered PVC (★) arising from an EAD island blocks superiorly (dashed line) but conducts inferiorly (solid line), subsequently reentering the blocked region to induce reentry. Beat #2 illustrates a scenario in which the triggered PVC arising from an EAD island encounters another EAD island, resulting in conduction block (dashed line) and reentry (solid lines). Adapted from Weiss et al. with permission.
Figure 4
Figure 4
Hypokalemia-induced positive feedback loops (red and blue arrows) promoting intracellular Na+ and Ca overload, CaMK activation and EADs during hypokalemia. The potentiation of the blue positive feedback loop by Class III antiarrhythmic (AA) drugs is also shown. INaK=Na+-K+ ATPase outward current. Reproduced with permission from Pezhouman et al .
Figure 5
Figure 5
Phase 2 reentry during simulated ischemia in canine epicardium. Traces show AP recordings from four sites (Epi 1–4) in a canine epicardial sheet exposed to simulated ischemia ([K+]o=6 mmol/l, hypoxia, pH=6.8). Sites 1 and 2 exhibit normal APs with accentuated AP domes, whereas sites 3 and 4 show early repolarization. Arrows show re-excitation of site 3 by the AP dome at site 2, inducing phase 2 reentry that self-terminates after 4 beats. Adapted from Lukas & Antzelevitch .
Figure 6
Figure 6
A. Schematic illustrating how APD shortening due to ATP-sensitive K+ current (IKATP) activation offsets net cellular K+ loss by decreasing the average driving force Em-EK for K+ efflux over the cardiac cycle. B. ADP shortening, conduction time (CT) delay, tension development and interstitial [K+]o accumulation versus time during acute global ischemia in rabbit ventricle. Reproduced from Weiss & Shine with permission.
Figure 7
Figure 7
Ventricular arrhythmias following injection of KCl (2.8 mg/kg) into the left anterior descending coronary artery of a dog. From Harris & Rojas with permission.
Figure 8
Figure 8
Initiation of reentry during acute ischemia. A. Injury current across the border zone (BZ) excites adjacent repolarized tissue in the non-ischemic zone (NIZ) to trigger a PVC (|) which propagates through the NIZ and reenters the ischemic zone (IZ) to initiate reentry. B. In ischemic subepicardial tissue, regions of all-or-none early repolarization with very short APD (blue) are juxtaposed to adjacent regions with normal APD and accentuated AP domes (red). The AP dome propagates into the repolarized region to trigger a closely coupled PVC (|) that propagates laterally until the normal AP region repolarizes and then reenters this region to initiate phase 2 reentry.
See this image and copyright information in PMC

References

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