Facilitation and Ca2+-dependent Inactivation Are Modified by Mutation of the Cav1.2 Channel IQ Motif

Abstract

The heart muscle responds to physiological needs with a short-term modulation of cardiac contractility. This process is determined mainly by properties of the cardiac L-type Ca

Mutation of the Calmodulin Binding Motif IQ of the L-type Cav1.2 Ca2+ Channel to EQ Induces Dilated Cardiomyopathy and Death

“…Because mice homozygous for the I/E mutation died early during embryogenesis (19) mice (20) and to mice expressing the tamoxifen-inducible Cre recombinase (MerCreMer (MCM)) under the control of the ␣-myosin heavy chain promoter (21). This line allows the cardio-specific induction of the Cre recombinase by tamoxifen injection in adult mice (21).…”

“…To clarify the physiological significance of the I/E mutation, we created a mouse line that carried the I1624E mutation in the Ca v 1.2 gene (19). Because mice homozygous for the I/E mutation died early during embryogenesis (19) mice (20) and to mice expressing the tamoxifen-inducible Cre recombinase (MerCreMer (MCM)) under the control of the ␣-myosin heavy chain promoter (21).…”

Truncation of Murine Cav1.2 at Asp-1904 Results in Heart Failure after Birth

“…Voltage-dependent facilitation of the channel requires in vitro and in vivo the CaM-KII dependent phosphorylation of Ser-1512 and Ser-1570 (16, 17). In addition, binding of CaM to the IQ motif located in the CCt is essential for Ca 2ϩ -dependent inhibition and facilitation of the channel (8,10,18,19).The distal CCt of the Ca V 1.2 channel (amino acids 1642-2143) has been reported to translocate to the nucleus and to modulate the transcription of several genes (20). Cleavage of the channel at residue 1623 does not result in a functional channel protein (21).…”

“…Voltage-dependent facilitation of the channel requires in vitro and in vivo the CaM-KII dependent phosphorylation of Ser-1512 and Ser-1570 (16, 17). In addition, binding of CaM to the IQ motif located in the CCt is essential for Ca 2ϩ -dependent inhibition and facilitation of the channel (8,10,18,19).…”

Deletion of the C-terminal Phosphorylation Sites in the Cardiac β-Subunit Does Not Affect the Basic β-Adrenergic Response of the Heart and the Cav1.2 Channel

“…Facilitation of I Ca was measured as described in Ref. 30. The stimulatory effect of isoproterenol (100 nmol/liter containing an equal concentration of ascorbic acid) on I Ca was examined after establishing a solid base line.…”