Key result
CaMKII inhibitors significantly depressed basal L-type Ca2+ channel activity to 26% of control, demonstrating that CaMKII activation is required to maintain basal channel activity in ventricular myocytes.
CaMKII activation is required for the maintenance of basal activity of L-type Ca2+ channels and prevents their run-down in guinea-pig ventricular myocytes.
CaMKII essential for basal L-type Ca2+ channel activity in myocytes; leaves open in vivo relevance and therapeutic targeting in disease.
The roles of calmodulin (CaM)-dependent protein kinase II (CaMKII) in the maintenance of basal activity and the reversion of run-down of L-type Ca2+ channels were studied in guinea-pig ventricular myocytes by the patch-clamp technique. In the cell-attached configuration, the Ca2+-channel activity was inhibited to 82% - 26% by 1-10 microM KN-93 and to 92% - 66% by 0.1-1 microM autocamtide-2-related inhibitory peptide (AIP) myristoylated. In the inside-out configuration, the bovine cardiac cytoplasm recovered Ca2+-channel activity to 87% of that recorded in the cell-attached configuration, while the CaMKII inhibitor 281-301 at 10 microM reduced the recovery effect to 19%. CaM + ATP recovered the channel activity to 93% and 28% of that recorded in the cell-attached configuration when applied at 1 and 5 min after run-down, respectively, showing a time-dependent attenuation. However, in the presence of 0.33 microM CaMKII, this attenuation was abolished, showing 85% and 75% recovery when applied at 1 and 5 min after run-down, respectively. This recovery effect was suppressed by 10 microM AIP, applied at 5 min, but not at 1 min after run-down. We concluded that CaMKII activation is required in the maintenance of basal activity of L-type Ca2+ channels.
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Hao et al. (2008) studied L-type Ca2+ channel run-down. CaMKII inhibitors (KN-93, AIP-m) vs. Control (vehicle or inactive analogue) was evaluated on Ca2+-channel activity (NPo) relative to control (p=<0.01). CaMKII inhibitors significantly depressed basal L-type Ca2+ channel activity to 26% of control, demonstrating that CaMKII activation is required to maintain basal channel activity in ventricular myocytes.
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