Disrupting Calcium Channel Expression To Lower Blood Pressure: New Targeting of a Well-Known Channel

Voltage-gated calcium channels in vascular smooth muscle cells (VSMCs) mediate many crucial Ca2+-dependent processes inherent to vascular biology including arterial contraction and gene expression. As such, they are intricately involved in the regulation of blood flow to critical organs and the determination of blood pressure levels. The VSMCs lack action potentials that form the basis for excitability in neuronal and cardiac cells. Instead, under physiological conditions, VSMCs show steady-state resting membrane potentials that fluctuate between-60 mV and-40 mV in response to vasoactive substances. Within this voltage range, membrane depolarization and the open-state probability of Ca2+ channels are positively and tightly coupled to regulate Ca2+ influx and vascular tone (1). Mathematical modeling suggests that at least several thousand pore-forming Ca2+ channel subunits are expressed in the plasma membrane of a single VSMC (2). The channels open but only slowly inactivate during sustained