Referenced in: none

Automatically associated channels: HCN3 , HCN4

Title: Myristoylated peptides potentiate the funny current (I(f)) in sinoatrial myocytes.

Authors: Zhandi Liao, Joshua R St Clair, Eric D Larson, Catherine Proenza

Journal, date & volume: Channels (Austin), 2011 Mar-Apr , 5, 115-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21150293

Abstract
The funny current, I(f), in sinoatrial myocytes is thought to contribute to the sympathetic fight-or-flight increase in heart rate. I(f) is produced by hyperpolarization-activated cyclic nucleotide sensitive-4 (HCN4) channels, and it is widely believed that sympathetic regulation of I(f) occurs via direct binding of cAMP to HCN4, independent of phosphorylation. However, we have recently shown that Protein Kinase A (PKA) activity is required for sympathetic regulation of I(f) and that PKA can directly phosphorylate HCN4. In the present study, we examined the effects of a myristoylated PKA inhibitory peptide (myr-PKI) on I(f) in mouse sinoatrial myocytes. We found that myr-PKI and another myristoylated peptide potently and specifically potentiated I(f) via a mechanism that did not involve PKA inhibition and that was independent of the peptide sequence, Protein Kinase C, or phosphatidylinositol-4,5-bisphosphate. The off-target activation of I(f) by myristoylated peptides limits their usefulness for studies of pacemaker mechanisms in sinoatrial myocytes.