Protein Kinase C Regulates Expression and Function of the Cav3.2 T-Type Ca2+ Channel during Maturation of Neonatal Rat Cardiomyocyte

Abstract

Two distinct isoforms of the T-type Ca2+ channel, Cav3.1 and Cav3.2, play a pivotal role in the generation of pacemaker potentials in nodal cells in the heart, although the isoform switches from Cav3.2 to Cav3.1 during the early neonatal period with an unknown mechanism. The present study was designed to investigate the molecular system of the parts that are responsible for the changes of T-type Ca2+ channel isoforms in neonatal cardiomyocytes using the whole-cell patch-clamp technique and mRNA quantification. The present study demonstrates that PKC activation accelerates the Ni2+-sensitive beating rate and upregulates the Ni2+-sensitive T-type Ca2+ channel current in neonatal cardiomyocytes as a long-term effect, whereas PKC inhibition delays the Ni2+-sensitive beating rate and downregulates the Ni2+-sensitive T-type Ca2+ channel current. Because the Ni2+-sensitive T-type Ca2+ channel current is largely composed of the Cav3.2-T-type Ca2+ channel, it is accordingly assumed that PKC activity plays a crucial role in the maintenance of the Cav3.2 channel. The expression of Cav3.2 mRNA was highly positively correlated with PKC activity. The expression of a transcription factor Nkx2.5 mRNA, possibly corresponding to the Cav3.2 channel gene, was decreased by an inhibition of PKCβII. These results suggest that PKC activation, presumably by PKCβII, is responsible for the upregulation of CaV3.2 T-type Ca2+ channel expression that interacts with a cardiac-specific transcription factor, Nkx2.5, in neonatal cardiomyocytes.

Role of curcumin in ischemia and reperfusion injury

“…6 Curcumin inhibits the Ca 2+ overload Ca 2+ overload plays an important role in the pathogenesis of IRI and it mainly occurs during reperfusion phase, of which the principal causes are the increased calcium influx, abnormal activation of protein kinase C (PKC) as well as cell membranes damage (Kashio et al, 2022;Wang et al, 2022). However, curcumin can inhibit IRI-induced Ca 2+ overload through targeting the mechanisms mentioned above.…”