Abstract 491: Triggered Sarcoplasmic Reticulum Ca Release Mediated By Na-ca Exchanger And Brain Na Channels In Rabbit Ventricular Cells
We tested the hypothesis that sarcoplasmic reticulum (SR) Ca release triggered by cardiac action potentials is significantly affected by Na influx through brain isoforms of the Na channel. These channels are reportedly located in the t-tubules and could therefore activate reverse Na-Ca exchanger (NCX) and contribute to triggered release. In the complete absence of a Na gradient (Li replacement) Ca transients evoked by action potentials were delayed, their upstrokes slowed and their peak values diminished (SR Ca content not depleted under these conditions). Ca spikes recorded under these conditions occurred at significantly lower probability and became asynchronous (see figure⇓). Tetrodotoxin 200 nM (this concentration selectively blocks brain Na channel isoforms Nav 1.1, 1.3 and 1.6) reduced the magnitude and rate of rise of Ca transients in a way that resembled the effect of removing the Na gradient. We suggest that early activation of brain type Na channels leads to elevation of Na in the dyadic cleft. This causes reverse NCX, which primes the junction with Ca before L-type Ca channels (LCC) have opened. Since the junction has been primed with Ca, short LCC openings can effectively gate ryanodine receptors (RyRs). Because these LCC openings have short latencies and occur with high probability they produce spikes with short latencies at high probability. In the absence of a Na gradient longer LCC openings are required to fill the junction and gate RyRs. These occur with lower probability and greater latency. We conclude that brain Na channels together with NCX significantly increase LCC-RyR coupling fidelity and synchronize spikes.