Studies of synaptic homeostasis during muscle fiber (MF) growth in Drosophila larvae have focused on the regulation of the quantal content of transmitter release. However, early studies in crayfish and frog suggested that regulation of quantal current size may be an integral mechanism in synaptic homeostasis. To examine this further in Drosophila, we compared the electrical properties, miniature excitatory postsynaptic potentials (minEPSPs) and miniature excitatory postsynaptic currents (minEPSCs) in different-sized MFs in third-instar larvae and for a single MF during larval growth. The third-instar MFs showed differences in input resistance due to differences in size and specific membrane resistance. We found that electrical coupling between MFs did not contribute substantially to the electrical properties; however, the electrode leak conductance and a slower developing increase in membrane conductance can influence the electrical recordings from these MFs. Our results demonstrated that larger MFs had larger minEPSCs to compensate for changes in MF electrical properties. This was most clearly seen for MF4 during larval growth from the second to third instar. During a predicted 80 % decrease in MF input resistance, the minEPSCs showed a 35 % increase in amplitude and 165 % increase in duration. Simulations demonstrated that the increase in minEPSC size resulted in a 129 % increase in minEPSP amplitude for third-instar larvae; this was mainly due to the increase in minEPSC duration. We also found that MFs with common innervation had similar-sized minEPSCs suggesting that MF innervation influences minEPSC size. Overall, the results showed that increased quantal content and quantal current size contribute equally to synaptic homeostasis during MF growth.

J wave syndrome (JWS) is an inherited cardiac channelopathy associated with malignant ventricular arrhythmias and sudden cardiac death (SCD), which comprises early repolarization syndrome and Brugada syndrome. Here, we explore the association between variants in the L -type calcium channel gene subunits, α 1C ( CACNA1C ) and β2b ( CACNB2b ), and the JWS phenotype. Using next-generation genetic sequencing of 402 JWS probands and their family members, we identified a CACNA1C -G37R (p.Gly37Arg) mutation in five individuals in four families, two of which had a family history of SCD as well as a CACNB2b -S143F (p.Ser143Phe) mutation in seven individuals in three families, two of which had a family history of SCD. The variants were located in exon 2 in CACNA1C and exon 5 in CACNB2b ; both were in highly conserved amino acid residues. Whole-cell patch-clamp results showed that compared with the wild-type group, calcium current density of CACNB2b- S143F and CACNA1C -G37R were significantly lower displaying a dominant-negative effect. Our findings provide further support for the hypothesis that variants in CACNA1C and CACNB2b are associated with JWS. The results suggest that mutations in these two genes lead to loss-of-function of the cardiac calcium channel current warranting their inclusion in genetic screening protocols. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

Repetitive stimulation of the Drosophila larval NMJ can produce a reduction in the frequency of miniature excitatory postsynaptic currents. By buffering postsynaptic Ca , it was shown that the decrease in "mini" frequency was due to an increase in postsynaptic Ca .