Adrenergic stimulation of rat resistance arteries affects Ca²⁺ sparks, Ca²⁺ waves, and Ca²⁺oscillations

Abstract

Confocal laser scanning microscopy and fluo 4 were used to visualize local and whole cell Ca(2+) transients within individual smooth muscle cells (SMC) of intact, pressurized rat mesenteric small arteries during activation of alpha1-adrenoceptors. A method was developed to record the Ca(2+) transients within individual SMC during the changes in arterial diameter. Three distinct types of "Ca(2+) signals" were influenced by adrenergic activation (agonist: phenylephrine). First, asynchronous Ca(2+) transients were elicited by low levels of adrenergic stimulation. These propagated from a point of origin and then filled the cell. Second, synchronous, spatially uniform Ca(2+) transients, not reported previously, occurred at higher levels of adrenergic stimulation and continued for long periods during oscillatory vasomotion. Finally, Ca(2+) sparks slowly decreased in frequency of occurrence during exposure to adrenergic agonists. Thus adrenergic activation causes a decrease in the frequency of Ca(2+) sparks and an increase in the frequency of asynchronous wavelike Ca(2+) transients, both of which should tend to decrease arterial diameter. Oscillatory vasomotion is associated with spatially uniform synchronous oscillations of cellular [Ca(2+)] and may have a different mechanism than the asynchronous, propagating Ca(2+) transients.

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

“…A water objective was used to obtain adequate working distance, as described previously (24). "Radial" confocal sections were used to image SMCs in cross section during active contractions (23). Individual SMCs can be successfully "tracked" during vasomotion by using radial sections.…”

“…It has been suggested that such asynchronous Ca 2ϩ waves, which arise from Ca 2ϩ released through inositol 1,4,5-trisphosphate receptors (InsP 3 R), are highly efficient in delivering Ca 2ϩ to MLCK that is tethered to the contractile myofilaments (20). 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).…”

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

“…Ca 2þ oscillations induced by norepinephrine were recorded over an 11 min time-window and during this period, the Ca 2þ spike frequency and amplitude decreased spontaneously (Figure 2A), resulting from receptor desensitization as reported by others. 30,31 The Ca 2þ oscillation frequency attained 2. 51 6 0.44 spikes/min measured over the last 3 min of norepinephrine exposure (n ¼ 8, P < 0.001 compared with control without norepinephrine, in which case the frequency was zero).…”

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

“…In some vessels, asynchronous oscillations of individual VSMC maintain a particular vascular tonus. However, in small resistance vessels the oscillations of groups of cells are synchronized through gap-junctions resulting in the pulsative contractile response [34,45,79,80]. This oscillatory activity can be regulated by variations of neurotransmitters following sympathetic activation and can affect contractile tone through the increase of frequency, thereby increasing blood flow or tissue oxygenation [43,45,46,81].…”