One of the most recognized characteristics of the L-type calcium channel is its unique sensitivity to 1,4-dihydropyridines (DHPs).
Unlike other voltage gated calcium channels, L-type calcium channels are resistant to ⍵-CT X (GVIA) and ⍵-AG A (IVA) inhibitory drugs.

A well observed form of modulation is due to alternative splicing.
A common form of modulation from alternative splicing is the C-terminal modulator (CTM).
It has a positively charged α-helix on the C-terminal called the DCRD and a negatively charged helix right after the IQ motif (CaM interaction site) called the PCRD.
The two helices can form a structure that bind competitively with CaM to reduce the open-state probability and lower calcium-dependent inhibition (CDI).

Alternative splicing is also seen on the β subunits to create different isoforms to give channels different properties due to palmitoylation and RNA editing.
Other forms of modulation on the β subunit include increasing or decreasing of the subunit's expression.
This is due to the fact that β subunits increase the open-probability of the channel, activity in the plasma membrane, and antagonize the ubiquitination of the channel.

L-type calcium channels are also modulated by G protein-coupled receptors and the adrenergic nervous system.
Protein Kinase A (PKA) activated by a G protein-coupled receptors cascade can phosphorylate L-type calcium channels, after channels form a signaling complex with A-Kinase-Anchoring proteins (AKAPs) , to increase calcium current through the channel, increasing the open-state probability, and an accelerated recovery period.
Activated Phospholipase C (PLC) from G protein-coupled receptors can breakdown polyphosphoinositides to decrease the channels calcium current by 20%-30%.


The adrenergic nervous system has been seen to modulate L-type calcium channels by cleaving the C-terminal fragment when the β-adrenergic receptor is stimulated to increase activation of the channels.
One of the most recognized characteristics of the L-type calcium channel is its unique sensitivity to 1,4-dihydropyridines (DHPs). Unlike other voltage gated calcium channels, L-type calcium channels are resistant to ⍵-CT X (GVIA) and ⍵-AG A (IVA) inhibitory drugs.
A well observed form of modulation is due to alternative splicing. A common form of modulation from alternative splicing is the C-terminal modulator (CTM). It has a positively charged α-helix on the C-terminal called the DCRD and a negatively charged helix right after the IQ motif (CaM interaction site) called the PCRD. The two helices can form a structure that bind competitively with CaM to reduce the open-state probability and lower calcium-dependent inhibition (CDI).
Alternative splicing is also seen on the β subunits to create different isoforms to give channels different properties due to palmitoylation and RNA editing. Other forms of modulation on the β subunit include increasing or decreasing of the subunit's expression. This is due to the fact that β subunits increase the open-probability of the channel, activity in the plasma membrane, and antagonize the ubiquitination of the channel.
L-type calcium channels are also modulated by G protein-coupled receptors and the adrenergic nervous system. Protein Kinase A (PKA) activated by a G protein-coupled receptors cascade can phosphorylate L-type calcium channels, after channels form a signaling complex with A-Kinase-Anchoring proteins (AKAPs) , to increase calcium current through the channel, increasing the open-state probability, and an accelerated recovery period. Activated Phospholipase C (PLC) from G protein-coupled receptors can breakdown polyphosphoinositides to decrease the channels calcium current by 20%-30%.

The adrenergic nervous system has been seen to modulate L-type calcium channels by cleaving the C-terminal fragment when the β-adrenergic receptor is stimulated to increase activation of the channels.
L-type calcium channel