The myogenic response is fundamental to blood flow regulation, particularly in brain where bulk perfusion is constrained. While L-type Ca 2 + channels (LTCCs) drive induction, questions remain to whether voltage is the sole means by which pressure controls their activity. In theory, pressure could also augment channel clustering so to amplify LTCC activity via a process termed functional coupling. It’s this idea that will be explored, herein. Whole-cell and cell-attached patch-clamp recordings revealed that pressure-like stimuli enhance LTCCs activity through a coordinated dual mechanism: (1) PKCα-dependent upregulation of functional coupling and (2) the recruitment of additional LTCC clusters from the perimembrane compartment. Super-resolution microscopy captured these dynamic cluster rearrangements and their spatial association with kinases governing pressure-induced functional coupling. Complementary pressure-myography experiments in mouse cerebral arteries with impaired functional coupling revealed a marked impairment of myogenic tone across the autoregulatory range, highlighting the physiological importance of this mechanism. These observations were reproduced in human cerebral vessels, and ensuing vascular network modeling showed that functional coupling is essential for maintaining appropriate perfusion distribution. Together, these findings position functional coupling as a central, tunable determinant of cerebrovascular tone and autoregulation. Fundings: Supported by the Canadian Institute for Health Research, National Institute of Health and the Rorabeck Chair in Vascular Biology and Neuroscience, CL & FS received funding from the Swiss National Science Foundation (Grant No. 200703 and 202199) and the Hartmann Müller Foundation (Grant No. 2885), MFN received funding from NIH R01HL171014 and R01HL180444. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Миронова et al. (Fri,) studied this question.