If at first you don't succeed try ... a new target in the treatment of angina.

Tardiff et al.¹ describe a promising new treatment forangina, ivabradine, that appears to selectively reduce heartrate by blocking the cardiac pacemaker ‘funny’ current,I_f. In contrast to the existing agents that slow heart rate,there is no accompanying intrinsic negative inotropic effect.Understanding the basis of this unique property requires a briefoverview of the underlying physiology. The cells of the sinoatrial node are the primary pacemaker ofthe heart. This function is the result of an upward, positive,depolarizing drift in their resting membrane potential duringthe diastolic phase of the action potential, known as the pacemakercurrent. Once this drift reaches a threshold potential, thenext action potential is triggered by the opening of slow calciumchannels and consequent influx of Ca²⁺ ions. Calcium antagonistsreduce Ca²⁺ influx through slow (L-type) calcium channels andthis leads to prolongation of the depolarization