Action potential subpopulations within human muscle sympathetic nerve activity: Discharge properties and governing mechanisms.

Abstract

Sympathetic emissions directed towards the skeletal muscle circulation - muscle sympathetic nerve activity (MSNA) - represent a key mechanism for maintaining homeostasis and supporting human survival during physiological stress. Pulse-rhythmic bursts formed by the synchronous discharge of differently-sized sympathetic action potentials (APs) represent the primary characteristic of MSNA. Of the APs firing under baseline conditions (reflecting low-threshold c-fibre activity), a range of subpopulations exists, of which three general categories can be discussed based on their peak-to-peak amplitude in the filtered raw neurogram - small, medium, and large. These subpopulations express nonuniform discharge, recruitment, and synchronization patterns. The subpopulation of medium APs fires synchronously in most bursts, while the subpopulations of small and large APs fire less often. However, 30% of total AP discharge occurs asynchronously between sympathetic bursts, a pattern expressed most often by small APs. In response to physiological stress (e.g., baroreflex unloading), the subpopulation of medium APs exhibits the largest increase in firing probability and a subpopulation of previously-silent larger and faster-conducting APs (reflecting high-threshold c-fibre activity) becomes recruited. Heterogeneous discharge, synchronization, and recruitment thresholds among AP subpopulations stem from differential regulation within the sympathetic organization including the arterial baroreflex and paravertebral ganglia. Indeed, the arterial baroreflex strongly regulates medium APs at baseline and enhances its control over this subpopulation during periods of baroreflex unloading. Conversely, small and large APs express weak baroreflex control. Trimethaphan infusion has revealed that ganglionic processes including nicotinic and non-nicotinic mechanisms may contribute to heterogenous firing behaviours among low-threshold AP subpopulations. This review highlights recent work revealing new insight to the discharge properties expressed by, and mechanisms governing, AP subpopulations within human MSNA.