parvalbumin α Inhibitors

The class of parvalbumin α inhibitors, despite its designation, does not consist of direct-acting small molecule inhibitors that bind to parvalbumin and inhibit its function. Instead, it encompasses a group of compounds that indirectly influence the activity of parvalbumin α by modulating intracellular calcium dynamics and signaling pathways that can alter the availability of calcium ions that parvalbumin is known to bind. These compounds function by affecting various calcium channels, receptors, and intracellular calcium stores to decrease the overall calcium concentration within the cell or specific subcellular compartments.

The indirect inhibitors include calcium channel blockers like nimodipine, which reduce calcium influx through L-type calcium channels, thereby limiting the calcium available for parvalbumin to bind and buffer. Ryanodine and dantrolene are agents that influence the ryanodine receptors involved in calcium release from the sarcoplasmic reticulum, whereas compounds like 2-APB and TMB-8 act on the inositol triphosphate (IP3) receptors to modulate calcium signaling. By altering the release of calcium from intracellular stores, these inhibitors could affect the buffering capacity of parvalbumin. Mibefradil and bepridil, by modulating T-type calcium channels and multi-channel activity, could impact the action potential firing patterns and the resultant intracellular calcium dynamics, which indirectly affects parvalbumin's role. Gabapentin, despite its primary use, can also affect neuronal excitability and, consequently, intracellular calcium levels, thereby having an indirect influence on parvalbumin α. Flunarizine, by decreasing intracellular calcium concentrations, can alter the environment in which parvalbumin operates, affecting its physiological role in neurons. Each compound in this class operates by influencing the calcium signaling pathways that govern parvalbumin's role in the cell, which includes its ability to bind calcium ions and its involvement in modulating the dynamics of calcium for proper cellular function.