https://www.cell.com/trends/neurosciences/pdf/0166-2236(88)90194-4.pdf

Multiple types of neuronal calcium channels and their selective modulation

Muscarinic receptors--characterization, coupling and function.

Receptor-effector coupling by G proteins

The voltage-dependent calcium current of many neurons is depressed by transmitters such as noradrenaline, GABA, and kappa-opiate agonists. This modulation probably constitutes a major mechanism of presynaptic inhibition. Although recent work has implicated GTP-binding proteins in the mechanism of current inhibition, it is still unknown how the activation of those proteins alters the operation of the channels. In their initial description of the phenomenon, Dunlap and Fischbach proposed that noradrenaline acts by somehow reducing the number of functions calcium channels in the cell. By contrast with this hypothesis, I have found that inhibition of Ca2+ current is primarily due to a transmitter-induced change in the voltage-dependence with which channels are opened. Transmitters profoundly alter the voltage-dependence of channel activation, but there is little or no change in the number of functional channels activated by very large depolarizations. There is also little effect on the voltage-dependence of inactivation.

Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence

A family of proteins called G proteins couples cell surface receptors to a variety of enzymes and ion channels. Since many cells contain several very similar G proteins, an important question is how signals remain specific as they cross the cell membrane.

Roles of G protein subunits in transmembrane signalling.

A possible direct effect of guanine nucleotide binding (G) proteins on calcium channels was examined in membrane patches excised from guinea pig cardiac myocytes and bovine cardiac sarcolemmal vesicles incorporated into planar lipid bilayers. The guanosine triphosphate analog, GTP gamma S, prolonged the survival of excised calcium channels independently of the presence of adenosine 39,59-monophosphate (cAMP), adenosine triphosphate, cAMP-activated protein kinase, and the protein kinase C activator tetradecanoyl phorbol acetate. A specific G protein, activated Gs, or its alpha subunit, purified from the plasma membranes of human erythrocytes, prolonged the survival of excised channels and stimulated the activity of incorporated channels. Thus, in addition to regulating calcium channels indirectly through activation of cytoplasmic kinases, G proteins can regulate calcium channels directly. Since they also directly regulate a subset of potassium channels, G proteins are now known to directly gate two classes of membrane ion channels.

https://science.sciencemag.org/content/sci/238/4831/1288.full.pdf

Yutaka Imoto

Papers

A G protein directly regulates mammalian cardiac calcium channels.