Genetic dissection of ion currents underlying all-or-none action potentials in C-elegans body-wall muscle cells

Non-technical summary Mammalian skeletal muscle contractions are initiated by all-or-none action potentials (APs) triggered by motoneurons. In C. elegans locomotory muscle, however, the characteristics of APs, the underlying ion channels, and their role in Ca2+ release are poorly understood. Here we show that C. elegans locomotory muscle fires spontaneous, all-or-none APs, which appear to be modulated by motoneuron activity. The upstroke of muscle APs requires Ca2+ entry through a voltage-gated Ca2+ channel (EGL-19), whereas the downstroke of the APs relies on a voltage-gated potassium channel as well as a Ca2+- and Cl--activated potassium channel. AP-elicited elevations of intracellular Ca2+ concentration require both EGL-19 in the plasma membrane and the ryanodine receptor in the sarcoplasmic reticulum membrane. The discovery of all-or-none action potentials in C. elegans body-wall muscle brings the physiology of C. elegans much closer to that of other metazoans, and strengthens its utility as a model organism. Abstract Although the neuromuscular system of C. elegans has been studied intensively, little is known about the properties of muscle action potentials (APs). By combining mutant analyses with in vivo electrophysiological recording techniques and Ca2+ imaging, we have established the fundamental properties and molecular determinants of body-wall muscle APs. We show that, unlike mammalian skeletal muscle APs, C. elegans muscle APs occur in spontaneous trains, do not require the function of postsynaptic receptors, and are all-or-none overshooting events, rather than graded potentials as has been previously reported. Furthermore, we show that muscle APs depend on Ca2+ entry through the L-type Ca2+ channel EGL-19 with a contribution from the T-type Ca2+ channel CCA-1. Both the Shaker K+ channel SHK-1 and the Ca2+/Cl--gated K+ channel SLO-2 play important roles in controlling the speed of membrane repolarization, the amplitude of afterhyperpolarization (AHP) and the pattern of AP firing; SLO-2 is also important in setting the resting membrane potential. Finally, AP-elicited elevations of [Ca2+](i) require both EGL-19 and the ryanodine receptor UNC-68. Thus, like mammalian skeletal muscle, C. elegans body-wall myocytes generate all-or-none APs, which evoke Ca2+ release from the sarcoplasmic reticulum (SR), although the specific ion channels used for AP upstroke and repolarization differ.