[Ca2+] changes in sympathetic varicosities and Schwann cells in rat mesenteric arteries—Relation to noradrenaline release and contraction

Abstract

AbstractAimThis 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.MethodsCa2+ 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.ResultsSchwann cells but not axons responded with a Ca2+ increase to ATP. Electrical field stimulation of nerves caused a frequency‐dependent increase in varicose [Ca2+] ([Ca2+]v). ω‐conotoxin‐GVIA (100 nmol/L) reduced the [Ca2+]v transient to 2 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 µmol/L), increased [Ca2+]v, noradrenaline release and force development both in the absence and presence of ω‐conotoxin‐GVIA. Yohimbine (1 µmol/L) increased both [Ca2+]v and noradrenaline release but reduced force development. Acetylcholine (10 µmol/L) 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.ConclusionModification 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.