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 E_m 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 al² with permission.