Hyperpolarization-activated cation currents: From molecules to physiological function

Hyperpolarization-activated cation currents, termed I-f, I-h, or I-q, were initially discovered in heart and nerve cells over 20 years ago. These currents contribute to a wide range of physiological functions, including cardiac and neuronal pacemaker activity, the setting of resting potentials, input conductance and length constants, and dendritic integration. The hyperpolarization-activated, cation nonselective (HCN) gene family encodes the channels that underlie I-h. Here we review the relation between the biophysical properties of recombinant HCN channels and the pattern of HCN mRNA expression with the properties of native I-h in neurons and cardiac muscle. Moreover, we consider selected examples of the expanding physiological functions Of Ih with a view toward understanding how the properties of HCN channels contribute to these diverse functional roles.