chronotrope

Chronotropy refers to the modulation of heart rate. A chronotrope is a substance or factor that alters the rate at which the sinoatrial node generates electrical impulses, thereby changing heart rate. The terms often distinguish positive chronotropic effects (increasing heart rate) from negative chronotropic effects (decreasing heart rate).

Most rapid adjustments of heart rate are mediated by the autonomic nervous system. Sympathetic stimulation releases norepinephrine which binds beta-1 adrenergic receptors in the SA node, increasing cAMP, enhancing the funny current (If) and calcium currents, and accelerating pacemaker depolarization. Parasympathetic input via the vagus releases acetylcholine, which activates muscarinic receptors M2, reduces cAMP, increases potassium conductance, and slows SA node firing. Intrinsic properties of the SA node, such as If, contribute to chronotropy independent of autonomic tone.

Pharmacologic chronotropes include positive agents such as isoproterenol, dobutamine, and epinephrine, as well as atropine, which blocks parasympathetic influence to raise heart rate. Negative chronotropes include beta-blockers and ivabradine, which blunt sympathetic stimulation or directly reduce SA node pacemaker activity.

Clinically, chronotropic response is relevant in contexts such as exercise testing and heart-rate control in arrhythmias or heart failure. Chronotropic incompetence refers to an inadequate heart-rate increase during effort, which can impair exercise capacity and prognosis. Understanding chronotropic mechanisms helps explain how drugs, disease, and autonomic balance shape the heart’s rate in health and illness.