Regulation of cardiac and smooth muscle Ca²⁺channels (Ca_V1.2a,b) by protein kinases

Abstract

High voltage-activated Ca(2+) channels of the Ca(V)1.2 class (L-type) are crucial for excitation-contraction coupling in both cardiac and smooth muscle. These channels are regulated by a variety of second messenger pathways that ultimately serve to modulate the level of contractile force in the tissue. The specific focus of this review is on the most recent advances in our understanding of how cardiac Ca(V)1.2a and smooth muscle Ca(V)1.2b channels are regulated by different kinases, including cGMP-dependent protein kinase, cAMP-dependent protein kinase, and protein kinase C. This review also discusses recent evidence regarding the regulation of these channels by protein tyrosine kinase, calmodulin-dependent kinase, purified G protein subunits, and identification of possible amino acid residues of the channel responsible for kinase regulation.

C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

“…Thus, we hypothesise that PKC-δ may act on MAP kinase phosphorylation following C-peptide exposure. At the same time, activated PKC-δ and -ɛ could phosphorylate and activate other downstream target proteins such as Ca 2+ channels [41,42]. L-Type Ca 2+ channels have been reported to be positively modulated by novel PKC isoforms [41,43] and it is established that C-peptide is capable of eliciting increases in intracellular Ca 2+ concentration [2,5,6].…”

“…At the same time, activated PKC-δ and -ɛ could phosphorylate and activate other downstream target proteins such as Ca 2+ channels [41,42]. L-Type Ca 2+ channels have been reported to be positively modulated by novel PKC isoforms [41,43] and it is established that C-peptide is capable of eliciting increases in intracellular Ca 2+ concentration [2,5,6]. In the present study we found that the Ca 2+ channel blockers verapamil and nifedipine abolished the effect of C-peptide on ERK1/2 phosphorylation, indicating that C-peptide stimulation results in an influx of Ca 2+ rather than in the release of intracellular Ca +2 stores.…”

Intraluminal Pressure Is a Stimulus for NFATc3 Nuclear Accumulation

“…Nitric oxide and cGMP-dependent kinase (PKG) have been traditionally viewed as mediators of vasodilation through effects on large conductance, Ca 2ϩ -activated potassium (BK) channels (26), VDCC (27,28), phospholamban (29), and IRAG inositol trisphosphate receptor-associated cGMP kinase substrate, as well as by decreasing the Ca 2ϩ sensitivity of the contractile process (30 -32). Recent evidence indicates that NO/ PKG can promote or inhibit vascular remodeling (33).…”

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

“…Protein kinases, such as PKA, PKC, and PKG, may modulate function of I Ca,L channel [23,24] . Some studies have reported that hyposmotic swelling modulates function of ion channels by changing activities of protein kinases, such as PKC, tyrosine protein kinase [8,17,25,26] .…”

“…Experiments utilizing direct activators of PKC have also demonstrated a range of effects on I Ca,L [23,24] . In this research, we observed that PKC activator (PMA) decreased the basal I Ca,L ( Figure 6) and PKC inhibitor (BIM) prevented the biphasic effects of hyposmotic swelling on I Ca,L (Figure 7).…”