2001). We used LCM to dissect cells under microscopy to avoid neuronal contamination. Our data also showed specific expression of HCN1 in the SAN, AVN and INE, but lack of expression in other areas of the heart, such as working atrial or ventricular myocytes. Both HCN4 and HCN1, involved in hyperpolarization-activated cation current, should be required for the generation of pacemaker
action potentials. A high expression of HCN4 and HCN1 might contribute PD-1/PD-L1 inhibitor 2 in part to a phase 4 automatic depolarization of INE. Low expression of HCN4 and HCN1 in working myocytes is consistent with a lack of automaticity. HCN2 was expressed in working myocytes but showed low expression in the SAN, AVN and INE. Yasui et al. (2001) found, in association with the mRNA subtype switch from HCN4 to HCN2, that the ventricle tends to lose If and pacemaker potency during the second half of embryonic development. At present, why HCN2 is expressed highly in working myocytes is worthy of further study. Different HCN isoforms can co-assemble. For
example, HCN1 and HCN2 have been co-expressed individually or in concatenated form in oocytes to yield functional channel proteins with properties distinct from those of the original channels (Ulens & Tytgat, 2000; Chen et al. 2001). Furthermore, recent evidence has indicated that the properties of If-channels Cobimetinib molecular weight of SAN
cells do not conform to specific features of the HCN isoforms expressed locally; activation kinetics and cAMP sensitivity of native pacemaker channels are intermediate between those reported for HCN1 and HCN4. Both HCN1 and HCN4 may contribute to native f-channels, but a context-dependent mechanism is also likely to modulate the channel properties in native tissues (Altmare et al. 2003). The results of our study show that different cardiac regions express different isoforms of the HCN family, which suggests that some of the native channel properties of the INE may be determined by co-assembly of different HCN isoforms into heteromers. The major calcium channel isoforms found in the heart are Cav1.2 (��1C), Cav1.3 (��1D), Cav3.1 (��1G) and Cav3.2 (��1H) (Catterall, 1995; Bohn et al. 2000; Perez-Reyes, 2003), so we detected two isoforms of the L-type channel ALG1 (Cav1.2 and Cav1.3) and two isoforms of the T-type (Cav3.1 and Cav3.2). The most prominently expressed T-type calcium channel in the INE was Cav3.1, whereas Cav3.2 was expressed at a moderate level. With the T-type calcium channel blocked completely, the heart rate is reduced by approximately 20%; if the density of the T-type calcium channel in cardiac pacing tissue is higher than normal, arrhythmias may be caused by the activation of the T-type channel (Chow et al. 2003). Mice with knockout of Cav3.
action potentials. A high expression of HCN4 and HCN1 might contribute PD-1/PD-L1 inhibitor 2 in part to a phase 4 automatic depolarization of INE. Low expression of HCN4 and HCN1 in working myocytes is consistent with a lack of automaticity. HCN2 was expressed in working myocytes but showed low expression in the SAN, AVN and INE. Yasui et al. (2001) found, in association with the mRNA subtype switch from HCN4 to HCN2, that the ventricle tends to lose If and pacemaker potency during the second half of embryonic development. At present, why HCN2 is expressed highly in working myocytes is worthy of further study. Different HCN isoforms can co-assemble. For
example, HCN1 and HCN2 have been co-expressed individually or in concatenated form in oocytes to yield functional channel proteins with properties distinct from those of the original channels (Ulens & Tytgat, 2000; Chen et al. 2001). Furthermore, recent evidence has indicated that the properties of If-channels Cobimetinib molecular weight of SAN
cells do not conform to specific features of the HCN isoforms expressed locally; activation kinetics and cAMP sensitivity of native pacemaker channels are intermediate between those reported for HCN1 and HCN4. Both HCN1 and HCN4 may contribute to native f-channels, but a context-dependent mechanism is also likely to modulate the channel properties in native tissues (Altmare et al. 2003). The results of our study show that different cardiac regions express different isoforms of the HCN family, which suggests that some of the native channel properties of the INE may be determined by co-assembly of different HCN isoforms into heteromers. The major calcium channel isoforms found in the heart are Cav1.2 (��1C), Cav1.3 (��1D), Cav3.1 (��1G) and Cav3.2 (��1H) (Catterall, 1995; Bohn et al. 2000; Perez-Reyes, 2003), so we detected two isoforms of the L-type channel ALG1 (Cav1.2 and Cav1.3) and two isoforms of the T-type (Cav3.1 and Cav3.2). The most prominently expressed T-type calcium channel in the INE was Cav3.1, whereas Cav3.2 was expressed at a moderate level. With the T-type calcium channel blocked completely, the heart rate is reduced by approximately 20%; if the density of the T-type calcium channel in cardiac pacing tissue is higher than normal, arrhythmias may be caused by the activation of the T-type channel (Chow et al. 2003). Mice with knockout of Cav3.
