cell membrane and have been seen to be anchored with a glycosylphosphatidylinositol (GPI) anchor. The γ subunit has eight isoforms (γ1-γ8) and is connected to the α1 subunit and has only been found in muscle cells in the CaV1.1 and CaV1.2 channels. Not much is known about the γ subunit, but it has been linked to interactions in hydrophobic forces. Mechanism Opening of the pore in L-type calcium channels takes place in the α1 subunit. When the membrane depolarizes, the S4 helix moves through the S4 and S5 linkers to the cytoplasmic ends of the S5 and S6 helices. This opens the activation gate which is formed by the inner side of the S6 helices in the α1 subunit. The most predominant way of autoinhibition of L-type calcium channels is with the /Cam complex. As the pore opens and causes an influx of calcium, calcium binds to calmodulin and then interacts with the loop that connects the adjacent EF-hand motifs and causes a conformational change in the EF-hand motif so it interacts with the pore to cause quick inhibition in the channel. It is still debated on where and how the pore and EF-hand interact. Hydrophobic pockets in the /Cam complex will also bind to three sections of the IQ domain known as the “aromatic anchors”. The /Cam complex has a high affinity towards L-type calcium channels, allowing it to get blocked even when there are low amounts of calcium present in the cell. The pore eventually closes as the cell repolarizes and causes a conformational change in the channel to put it in the closed conformation. Inhibition and modulation 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