Extracellular calcium chelation and attenuation of calcium entry decrease in vivo cholinergic‐induced eccrine sweating sensitivity in humans

New Findings What is the central question of this study? Calcium is an important second messenger in eccrine sweating; however, whether modulation of extracellular Ca2+ and Ca2+ entry has the capacity to modulate sweat rate in non-glabrous human skin has not been explored. What is the main finding and its importance? Acetylcholine to sweat rate dose–response relationships identify that local in vivo Ca2+ chelation and L-type Ca2+ channel antagonism have the capacity to attenuate the cholinergic sensitivity of eccrine sweat glands. Importantly, these data translate previous glabrous in vitro animal studies into non-glabrous in vivo human skin. Calcium is an important second messenger in eccrine sweating, with both internal and external sources being identified in vitro. It is unclear whether in vivo modulation of extracellular Ca2+ levels or influx has the capacity to modulate sweat rate in non-glabrous human skin. To test the hypothesis that lowering interstitial Ca2+ levels would decrease the sensitivity of the ACh to sweat rate (via capacitance hygrometry) dose–response relationship, nine healthy subjects received six ACh doses (1 × 10−5 to 1 × 100 m in 10-fold increments) with and without a Ca2+ chelator (12.5 mg ml−1 EDTA) via forearm intradermal microdialysis (protocol 1). To test the hypothesis that attenuating Ca2+ influx via L-type Ca2+ channels would also decrease the sensitivity of the ACh to sweat rate dose–response relationship, 10 healthy subjects received similar ACh doses with and without a phenylalkylamine Ca2+ channel blocker (1 mm verapamil; protocol 2). Non-linear regression curve fitting identified a right-shifted ED50 in EDTA-treated sites compared with ACh alone (−1.0 ± 0.1 and −1.5 ± 0.1 logm, respectively; P   0.05) in protocol 1. Protocol 2 also resulted in a right-shifted ED50 (verapamil, −0.9 ± 0.1 logm; ACh alone, −1.6 ± 0.2 logm; P   0.05). Thus, local in vivo Ca2+ chelation and L-type Ca2+ channel antagonism have the capacity to attenuate in vivo cholinergic sensitivity of eccrine sweat glands. These data suggest that interstitial Ca2+ and its influx via Ca2+ channels play a functional role in eccrine sweating in intact non-glabrous human skin.