Ca²⁺ changes in sympathetic varicosities and Schwann cells in rat mesenteric arteries - relation to noradrenaline release and contraction

Aim: This study aimed to assess intracellular Ca²⁺ dynamics in nerve cells and Schwann cells in isolated rat resistance arteries and determine how these dynamics modify noradrenaline release from the nerves and consequent force development.

Methods: Ca²⁺ in nerves was assessed with confocal imaging, noradrenaline release with amperometry, and artery tone with wire myography. Ca²⁺ in axons was assessed after loading with Oregon Green 488 BAPTA‐1 dextran. In other experiments, arteries were incubated with Calcium Green‐1‐AM which loads both axons and Schwann cells.

Results: Schwann cells but not axons responded with a Ca²⁺ increase to ATP. Electrical field stimulation of nerves caused a frequency dependent increase of varicose [Ca²⁺] ([Ca²⁺]_v). ω‐conotoxin‐GVIA (100 nM) reduced the [Ca²⁺]_v transient to 2 Hz and 16 Hz by 60% and 27%, respectively; in contrast ω‐conotoxin GVIA inhibited more than 80% of the noradrenaline release and force development at 2 and 16 Hz. The KV channel blocker, 4‐aminopyridine (10 μM), increased [Ca²⁺]_v, noradrenaline release, and force development both in the absence and presence of ω‐conotoxin‐GVIA. Yohimbine (1 μM) increased both [Ca²⁺]_v and noradrenaline release but reduced force development. Acetylcholine (10 μM) caused atropine‐sensitive inhibition of [Ca²⁺]_v, noradrenaline release and force. In the presence of ω‐conotoxin‐GVIA, acetylcholine caused a further inhibition of all parameters.

Conclusion: Modification of [Ca²⁺] in arterial sympathetic axons and Schwann cells was assessed separately. KV3.1 channels may be important regulators of [Ca²⁺]_v, noradrenaline release, and force development. Presynaptic adrenoceptor and muscarinic receptor activation modify transmitter release through modification of [Ca²⁺]_v.