Regulation of L-type Ca2+ channels in the heart: overview of recent advances

Kaoru Yamaoka1, Masaki Kameyama

  • 1Department of Physiology, School of Medicine, Hiroshima University, Minami-Ku, Hiroshima, Japan. kyamaok@hiroshima-u.ac.jp

Insights

This review explores how L-type Ca2+ channels in the heart are regulated by factors like phosphorylation and magnesium (Mg2+). It details mechanisms influencing channel activity and cardiac function.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Ion Channel Function

Background:

  • L-type Ca2+ channels are crucial for cardiac function.
  • Their regulation is complex, involving multiple interacting factors.
  • Understanding these factors is key to understanding cardiac electrophysiology.

Purpose of the Study:

  • To review the key regulatory mechanisms of cardiac L-type Ca2+ channels.
  • To elucidate the roles of c-AMP dependent phosphorylation and magnesium (Mg2+).
  • To discuss the phenomenon of channel run-down and its implications.

Main Methods:

  • Literature review of recent molecular and physiological studies.
  • Analysis of experimental data on L-type Ca2+ channel activity.
  • Synthesis of information on channel regulation.

Main Results:

  • c-AMP dependent phosphorylation significantly modulates channel activity.
  • Magnesium ions (Mg2+) play a critical role in channel gating and function.
  • Channel run-down is a complex process affecting channel availability.

Conclusions:

  • Cardiac L-type Ca2+ channel regulation involves intricate interplay of phosphorylation, divalent cations, and other factors.
  • Detailed understanding of these mechanisms is essential for cardiac health.
  • Further research is needed to fully unravel channel regulation complexities.

Related Concept Videos

Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...