The three mouse HCN genes (mHCN1, 2, and 4) show distinct and complementary patterns of mRNA expression across the CNS, which correlates with the functional heterogeneity of native Ih currents.
The functional diversity of hyperpolarization-activated pacemaker (I(h)) channels in the mouse CNS is partly driven by the differential expression of HCN gene isoforms.
The hyperpolarization-activated cation current (termed I(h), I(q), or I(f)) was recently shown to be encoded by a new family of genes, named HCN for hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective. When expressed in heterologous cells, each HCN isoform generates channels with distinct activation kinetics, mirroring the range of biophysical properties of native I(h) currents recorded in different classes of neurons. To determine whether the functional diversity of I(h) currents is attributable to different patterns of HCN gene expression, we determined the mRNA distribution across different regions of the mouse CNS of the three mouse HCN genes that are prominently expressed there (mHCN1, 2 and 4). We observe distinct patterns of distribution for each of the three genes. Whereas mHCN2 shows a widespread expression throughout the CNS, the expression of mHCN1 and mHCN4 is more limited, and generally complementary. mHCN1 is primarily expressed within neurons of the neocortex, hippocampus, and cerebellar cortex, but also in selected nuclei of the brainstem. mHCN4 is most highly expressed within neurons of the medial habenula, thalamus, and olfactory bulb, but also in distinct neuronal populations of the basal ganglia. Based on a comparison of mRNA expression with an electrophysiological characterization of native I(h) currents in hippocampal and thalamic neurons, our data support the idea that the functional heterogeneity of I(h) channels is attributable, in part, to differential isoform expression. Moreover, in some neurons, specific functional roles can be proposed for I(h) channels with defined subunit composition.
Santoro et al. (Sat,) reported a other. HCN channel expression and electrophysiological characterization was evaluated on Distribution of mHCN1, mHCN2, and mHCN4 mRNA and biophysical properties of Ih currents. The three mouse HCN genes (mHCN1, 2, and 4) show distinct and complementary patterns of mRNA expression across the CNS, which correlates with the functional heterogeneity of native Ih currents.