@entity943 are often associated with mutations in ion channels or other proteins. To enable drug development for distinct @entity943 , model systems are required that allow implementing @entity1 -specific mutations. We assessed a muscular pump in @entity2199 . The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining @entity1 cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms-EPGs), and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated @entity141 -channel) @entity40930 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with @entity1162 . @entity40930 mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate @entity943 in the optogenetically paced pharynx. The @entity7236 analog @entity68457 prolonged pump duration in wild type, and reduced or prolonged pump duration of distinct @entity40930 alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations, and permit to better understand the effects of distinct mutations on a macroscopic level.

Arrhythmogenic effects of mutated L-type XXXX -channels on an optogenetically paced muscular pump in @entity2199 .

@entity1 :: ('9606', 'Species') :: ['human', 'patient'] @entity2199 :: ('6239', 'Species') :: ['Caenorhabditis elegans'] @entity7236 :: ('MESH:C038806', 'Chemical') :: ['dihydropyridine'] @entity68457 :: ('MESH:C510591', 'Chemical') :: ['Nemadipine A'] @entity40930 :: ('177513(Tax:6239)', 'Gene') :: ['EGL-19', 'egl-19'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1162 :: ('MESH:D008133', 'Disease') :: ['long QT syndrome'] @entity943 :: ('MESH:D001145', 'Disease') :: ['arrhythmias', 'arrhythmia', 'Cardiac arrhythmias']
@entity141 :: (CHEBI:29108,Chemical) :: ['Ca(2+)']
