Abstract

This chapter provides highlights of the history regarding the discovery of the native cardiac current (If) and describes its unusual biophysical nature and modulation related to its important physiological role in pacemaking. The current, If, has now been generally accepted to play an important role in the generation and modulation of pacemaking in the SA node and other conduction tissue. If is inward and activates on hyperpolarization at the termination of an action potential, and is substantially activated when the membrane potential approaches the maximum diastolic potential in the range of 65–70 mV. Its slow kinetics is compatible with the generation of a slow voltage depolarization of an approximately constant slope. Modulation is achieved by the shifting of the activation curve along the voltage axis, a mechanism that can be controlled in a very precise manner by altering the intracellular levels of cAMP and hence, controlling heart rate. If is found in the ventricle and atrium, but its function under normal conditions in the adult mammal seems limited. However, If may play a role in the excitability of these tissues in the developing animal that display a greater functional expression of the current. The presence of If in the atrium and its modulation by antiarrhythmic drugs in this tissue suggest a role in physiology and pathophysiology of atrial excitability. Receptors for a glucagon-like peptide have also been shown to exist in the heart, which demonstrates that both glucagon and GLP are probable modulators of the pacemaker current activation curve. The action of adenosine on If is very important, given the use of this agent in clinical situations for improvement of conduction through the AV node.

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