We recently discovered that the constitutively active Src tyrosine kinase can enhance
hyperpolarization-activated, cyclic nucleotide-gated (HCN) 4 channel activity by binding to
the channel protein. To investigate the mechanism of modulation by Src of HCN channels,
we studied the effects of a selective inhibitor of Src tyrosine kinase, 4-amino-5-(4-
chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyrimidine (PP2), on HCN4 and its mutant
channels expressed in HEK 293 cells by using a whole cell patch-clamp technique. We …

We recently discovered that the constitutively active Src tyrosine kinase can enhance the
HCN4 channel activity by binding to the channel protein. To investigate the mechanism of
modulation by Src of HCN channels, we studied the effects of a selective inhibitor of Src
tyrosine kinase, PP2, on HCN4 and its mutant channels expressed in HEK293 cells using
wholecell patch clamp technique. We found that PP2 can inhibit HCN4 currents by
negatively shifting the voltage dependence of channel activation, decreasing the whole-cell …