Information for the community

Voltage-gated calcium channels (VGCCs) are a group of proteins found in the membrane, or boundary, of a cell. They have the crucial role of supporting how cells communicate with each other. These calcium channels, also known as CaVs, are found in the brain, heart, and muscles, where cells communicate with each other by sending information in the form of electrical signals.

 

The primary function of these calcium channels is to allow calcium ions into a cell in response to these electrical signals and pass the information on to neighboring cells. For example, in brain cells called neurons, neurotransmitters (chemical messengers) are physically transported to neighboring neurons when the electrical signals reach the end of the cell where the calcium channels reside (Figure 1).

 

The channels detect the signal and open to let calcium ions inside. This, in turn, tells the neuron to package up its neurotransmitters and send them to the next neuron, where a new electrical signal is induced. This process repeats rapidly, over and over again, and allows information to be sent through the brain and to the rest of the body so that we can walk, talk, run, learn, eat, etc.

What do voltage-gated calcium channels look like?

 

The CaV channels are composed of a main subunit called CaVα1 (alpha one), which forms the pore or channel in the membrane. There are also additional subunits, CaVβ (beta), CaVα2δ (alpha two delta), and CaVγ (gamma) that can sometimes physically interact with the alpha one subunit (Figure 2).

 

These subunits can help transport the alpha one subunit to the end of neurons or help control how the channel opens or closes. Sometimes these subunits can also physically interact with chemical compounds or medicines to influence calcium channel activity. 

The human genome has 10 genes that contain instructions to make the CaV calcium channels (see table below). The calcium channel superfamily is split into three groups: CaV1, CaV2, and CaV3 based on specific properties.

How do voltage-gated calcium channels work?

 

The structure of these calcium channels is crucial to how the channels function. All ten CaV alpha one subunits share a common structure, with four major transmembrane (membrane-spanning) domains known as Domain I through IV.

 

The 2-D structure is shown in Figure 3. Within each domain, there are six transmembrane subunits denoted as S1 through S6. S4 is the main subunit responsible for detecting the electrical signal traveling down the neuron, with assistance from S1-S3. S5 and S6 are the transmembrane subunits responsible for creating the hole in the membrane.

 

There are loops that connect the domains and subunits, some of which are very important for the channel function. For example, the loop between S5 and S6 in each domain is called the “re-entrant p-loop” that is responsible for making sure that only calcium ions enter the channel.