Invited Review: Arteriolar smooth muscle mechanotransduction: Ca²⁺signaling pathways underlying myogenic reactivity

Abstract

The smooth muscle of arterioles responds to an increase in intraluminal pressure with vasoconstriction and with vasodilation when pressure is decreased. Such myogenic vasoconstriction provides a level of basal tone that enables arterioles to appropriately adjust diameter in response to neurohumoral stimuli. Key in this process of mechanotransduction is the role of changes in intracellular Ca(2+). However, it is becoming clear that considerable complexity exists in the spatiotemporal characteristics of the Ca(2+) signal and that changes in intracellular Ca(2+) may play roles other than direct effects on the contractile process via activation of myosin light-chain phosphorylation. The involvement of Ca(2+) may extend to modulation of ion channels and release of Ca(2+) from the sarcoplasmic reticulum, alterations in Ca(2+) sensitivity, and coupling between cells within the vessel wall. The purpose of this brief review is to summarize the current literature relating to Ca(2+) and the arteriolar myogenic response. Consideration is given to coupling of Ca(2+) changes to the mechanical stimuli, sources of Ca(2+), involvement of ion channels, and spatiotemporal aspects of intracellular Ca(2+) signaling.

Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries

“…Consistent with this notion is evidence that in ovine fetal cerebral arteries norepinephrineinduced contractions occur primarily due to Ca 2ϩ influx, whereas in adults Ca 2ϩ released from intracellular stores also contributes (35). Whether, in addition to depolarization, mechanosensitive elements directly signal pressure-induced voltagedependent Ca 2ϩ channel activation in the newborn cerebrovasculature cannot be concluded from our study (21,36). In newborn cerebral arteries, pressure-induced constriction is Ca 2ϩ dependent.…”

“…Another potential mechanism is that integrins, a family of membrane-spanning glycoproteins, mechanotransduce changes in intravascular pressure to voltagedependent Ca 2ϩ channel activity (21,36). In addition, intravascular pressure may also activate Ca 2ϩ influx via alternative pathways, including store-operated or capacitative Ca 2ϩ entry (45,59).…”

Atherosclerosis-related molecular alteration of the human Ca V 1.2 calcium channel α 1C subunit

“…These findings raise an interesting possibility that some Ca v 1.2 channel isoforms are less sensitive to Ca 2ϩ -induced inactivation that controls both the slow inactivation (33) and run-down of the channel (34). Because ␣ 1C,125 and ␣ 1C,127 are able to maintain a more sustained Ca 2ϩ flux, they may have a specific role in VSMC functions that require prolonged Ca 2ϩ influx, such as the maintenance of vascular tone and elasticity of arterial walls (35).…”

Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction

“…In some small arteries, a different type of contractile Ca 2ϩ signal also may be generated, particularly when levels of receptor activation are high: Ca 2ϩ oscillations that are spatially uniform and synchronized among the different cells (6,23 ] (15, 27) but also, importantly, involves increased activity of certain protein kinases, possible transactivation of extracellular growth factor receptor, activity of the local renin-angiotensin system (RAS), and other enzymes (for review on mechanisms of MT, see Ref. 7). Surprisingly, however, it was not known previously whether ␣ 1 -adrenoceptor-induced Ca 2ϩ signals in such arteries were of the type described above or whether they might be different, due to the markedly different state of the cell once MT has developed.…”