Imaging sympathetic neurogenic Ca²⁺ signaling in blood vessels

We review the information that has been provided by optical imaging experiments directed at understanding the role and effects of sympathetic nerve activity (SNA) in the functioning of blood vessels. Earlier studies utilized electric field stimulation of nerve terminals (EFS) in isolated arteries and vascular tissues (ex vivo) to elicit SNA, but more recently, imaging studies have been conducted in vivo, enabling the study of SNA in truly physiological conditions. Ex vivo: In vascular smooth muscle cells (VSMC) of isolated arteries, the three sympathetic neurotransmitters, norepinephrine (NE), ATP and neuropeptide Y (NPY), elicit or modulate distinct patterns of Ca²⁺ signaling, as revealed by confocal imaging of exogenous fluorescent Ca²⁺ indicators. Purinergic junctional Ca²⁺ transients (jCaTs) arise from Ca²⁺ influx during excitatory junction potentials (eJPs), and are associated with the initial neurogenic contraction. Adrenergic Ca²⁺ waves and oscillations cause contraction while SNA-induced endothelial Ca²⁺ 'pulsars' cause relaxation. In vivo: optical biosensor mice, which express genetically encoded Ca²⁺ indicators (GECI's) specifically in smooth muscle, combined with non-invasive imaging techniques has enabled imaging SNA-induced Ca²⁺ signaling and arterial diameter in vivo. SNA induces Ca²⁺ oscillations in intact arteries. [Ca²⁺] of arterial smooth muscle cells increased in hypertension, in association with increased SNA. High resolution imaging has revealed local sympathetic, neurogenic Ca²⁺ signaling within smooth muscle and endothelial cells of the vasculature. The ongoing development of in vivo imaging together with an expanding availability of different biosensor animals promises to enable the further assessment of SNA and its effects in the vasculature of living animals.