The cell membrane is relatively impermeable to sodium ions (Na⁺), and cells expend much energy pumping Na⁺ out of cells to maintain higher extracellular Na⁺ concentrations and negative resting membrane potentials (about −90 mV in heart muscle). The organized influx of Na⁺ back into cardiac cells through Na⁺ channels, however, helps pacemaker cells reach threshold; allows propagation of the action potential through the heart's conduction system and muscle; and triggers calcium influx in myocardium, which in turn initiates myocardial contraction.

Many pharmaceutical agents are administered primarily because of their ability to block Na⁺ channels, whereas other Na⁺ channel antagonists are given because of additional pharmacologic effects (Table 1). The ability of agents to block Na⁺ channels is variously described as a membrane stabilizing effect, a local anesthetic effect, or a quinidine-like effect. Regardless of which name is used, toxicity following large doses of Na⁺ channel blockers shares a common pathophysiology and results in similar signs and symptoms. Importantly, recent studies indicate that adverse effects resulting from Na⁺ channel blockade produced by a multitude of agents may respond to therapy with hypertonic sodium bicarbonate.