Structural bases of inhibitory mechanism of Ca_V1.2 channel inhibitors.

ABSTRACT: The voltage-gated calcium channel Ca_V1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of Ca_V1.2 are involved in brain and heart diseases. Pharmacological inhibition of Ca_V1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of Ca_V1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6^II, S6^III, and S6^IV helices and forms extensive hydrophobic interactions with Ca_V1.2. Our structure elucidates that benidipine is located in the D_III-D_IV fenestration site. Its hyd

SUBMITTER: Wei Y 

PROVIDER: S-EPMC10981686 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature