The C. elegans T-type calcium channel CCA-1 boosts neuromuscular transmission.
Low threshold-activated or T-type calcium channels are postulated to mediate a variety of bursting and rhythmic electrical firing events. However, T-type channels' exact physiological contributions have been difficult to assess because of their incompletely defined pharmacology and the difficulty in isolating T-type currents from more robust high threshold calcium currents. A current in C. elegans pharyngeal muscle displays the kinetic features of a T-type calcium channel and is absent in animals homozygous for mutations at the cca-1 locus (see accompanying paper). cca-1 is expressed in pharyngeal muscle and encodes a protein (CCA-1) with strong homology to the alpha1 subunits of vertebrate T-type channels. We show that CCA-1 plays a critical role at the pharyngeal neuromuscular junction, permitting the efficient initiation of action potentials in response to stimulation by the MC motor neuron. Loss of cca-1 function decreases the chance that excitatory input from MC will successfully trigger an action potential, and reduces the ability of an animal to take in food. Intracellular voltage recordings demonstrate that when wild-type cca-1 is absent, the depolarizing phase of the pharyngeal action potential tends to plateau or stall near -30 mV, the voltage at which the CCA-1 channel is likely to be activated. We conclude that the CCA-1 T-type calcium channel boosts the excitatory effect of synaptic input, allowing for reliable and rapid depolarization and contraction of the pharyngeal muscle. We also show that the pharyngeal muscle employs alternative strategies for initiating action potentials in certain cases of compromised MC motor neuron function.
Steger
Katherine A
KA
Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.
Shtonda
Boris B
BB
Thacker
Colin
C
Snutch
Terrance P
TP
Avery
Leon
L
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005838:Genotype; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology; D010641:Phenotype
D029742:Caenorhabditis elegans Proteins; D020747:Calcium Channels, T-Type