Abstract
The funny or hyperpolarization-activated cyclic nucleotide-gated channel (HCN) modulates cardiac excitability and heart rate by regulating the If or IKf current in sinoatrial cells.1 The 4 HCN channel isoforms (HCN1–4) are unique in that they are activated by both cyclic adenosine monophosphate (AMP) and hyperpolarized membrane channels. Thus, sympathetic activation of β-adrenergic receptors (β-AR) on the cardiac sarcolemma and the resultant increase in cellular levels of cyclic AMP shift the activation potential of the channel thereby increasing heart rate. Channel activity is also modified by phosphoinositides including phosphatidylinositol-4,5-bisphosphate and by Src kinase–mediated phosphorylation in an isoform-specific manner.2 HCN channels also play a role in regulating excitability in neurons, and changes in channel activity have been associated with the development of epilepsy and seizures.3
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