Worm Breeder's Gazette 13(2): 50 (February 1, 1994)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Of the 14 neuron types in the pharynx, MC is the most important for muscle excitation since when it is killed, pharyngeal pumping rate is reduced 4-5 told. Two mechanisms could explain how MC excites the pharynx, a myogenic mechanism (M) and a neurogenic mechanism (N). In the myogenic mechanism, timing of pumps is controlled by the muscle and MC modulates the excitability of the muscle. In the neurogenic mechanism, timing of pumps is controlled by MC directly.
M: The rhythm of the pharynx is clearly myogenic. MC just makes the muscle more excitable. MC is to the pharynx what sympathetic neurons are to the mammalian heart. They make the heart beat faster by modulating pacemaker currents in the muscle. Like the mammalian heart, the pharynx can pump without its nervous system so it must function myogenically.
N: Your logic is flawed. The capability for a myogenic rhythm doesn't prove that the rhythm is myogenic when the nervous system is present. The leech heart tube rhythm is an example of a system that can be myogenic when its innervation is severed but is controlled by neuronal activity in the intact animal. In the C. elegans pharynx, it's likely that the myogenic mechanism is just a backup for MC, and that the rhythm is normally neurogenic. The timing of pumps is controlled by excitatory postsynaptic potentials (EPSPs) transmitted by MC. This is like the mammalian motor system where EPSPs transmitted by motor neurons trigger skeletal muscle contractions.
M: Doesn't look like I'll convince you with behavioral data. What about elecrophysiology?
N: Glad you brought that up! The EPG (electropharyngeogram) consists of four phases: E, P, R, and I. The E-phase and R-phase spikes are caused by pharyngeal muscle depolarization and repolarization respectively and the P-phase spikes are caused by inhibitory synaptic transmission between pharyngeal neuron M3 and the muscle. The I-phase spikes are key here. The I- (for interpump) phase has rare positive spikes that don't correlate with perceptible pharyngeal motion. Since the polarity of these spikes is positive, in the direction of muscle depolarization, they must represent synaptic transmission between MC and the muscle. Indeed, when MC is killed, these rare I-phase spikes are eliminated. Also, the first E-phase transient is greatly reduced or eliminated when you kill MC. This makes perfect sense. The rare I-phase transient is an ineffective MC EPSP, one that failed to trigger a pump, and the I-phase is a combination of an effective MC EPSP and the depolarization of a muscle action potential that it triggered.
M: Not convinced. Your reasoning works just as well for a myogenic mechanism--Just replace 'MC" with "muscle pacemaker cell". The rare I-phase transient is an ineffective action potential in a pacemaker muscle cell, one that failed to trigger a pump, and the E-phase is a combination of an effective action potential in the pacemaker muscle cell and the depolarization phase of the synchronous action potentials in other pharyngeal muscle cells. MC just modulates the activity of the muscle pacemaker cell. The only way to convince me that the rhythm is neurogenic is to record from MC and show that its activity correlates with the I-phase spikes.
N: That's cheap. You know we can't record from MC. Ah, I almost forgot! What about the EPG of snt-1 ,a mutant which lacks synaptotagmin? In this EPG, between the rare pumps, there are periodic bursts of I-phase spikes. MC is necessary and sufficient for these spikes. Since synaptotagmin is expressed in neurons at synapses, these bursts must be caused by the defective synaptic activity of MC. This synaptic transmission is extremely inefficient at triggering pumps. You're very quiet. Are you finally convinced?
M: Well, OK. I guess it would be difficult to explain the snt-1 EPG with a myogenic mechanism. But wouldn't you buy that even with MC intact, a myogenic rhythm is used sometimes? For instance, the EPG of a pharynx that is pumping slowly looks just like the EPG of an MCø worm: there are no I-phase spikes and the first E-phase spike is small or absent. I'll use the heart as an analogy again. Usually the heartbeat is initiated in the SA node but sometimes ectopic beats can originate in other parts of the heart. I n this analogy "SA node" = MC, and "other parts of the heart" = pharyngeal muscle.
N: I'll buy that without recording from MC, there's no way to rule that out.
M: I still have two problems with MC being the pacemaker for the muscle. How do you
explain the fact that it synapses on marginal cells and not on muscle cells? And how are the activities of the two MCs coordinated without gap junctions between them?
N: Both are good questions. To answer the first, it's possible that marginal cells are gap functioned to muscle cells so that EPSPs in marginal cells are also effective in the muscle cells. Indeed, David Hall saw gap junctions between marginal cells and muscle cells. To answer the second, I could speculate blindly but will hold off until we know more.
