A mechanism for graded motor control encoded in the channel properties of the muscle ACh receptor

The larva of the invertebrate chordate Ciona intestinalis possesses only 36 striated muscle cells and lacks body segmentation. It can swim, however, like a vertebrate tadpole, and how its simple body achieves such sophisticated motor control remains puzzling. We found that muscle contractions in Ciona larvae are variable and can be changed by sensory stimuli, so that neuromuscular transmission can convert the variable neural inputs into graded muscle activity. We characterized the molecular nature of the nicotinic acetylcholine receptor (nAChR) at neuromuscular synapses. When heterologously expressed in Xenopus oocytes, this nAChR channel exhibited two biophysical features resembling vertebrate neuronal nAChRs rather than the muscle type: inward rectification and high Ca(2+) permeability. Both of these properties were abolished by a simple mutation at the channel pore in one of the non-α subunits, called BGDE3, so as to adopt the sequence of related subunits in vertebrates, γ and ε. In vivo exchange of native BGDE3 with this mutant severely disrupted graded motor control, producing instead sporadic all-or-none-like flexions. The graded nature of excitation-contraction (E-C) coupling in this organism is based on the traits of the nAChR channel pore, which confer fine controllability on such a coarse motor architecture.