Effect of ryanodine on sinus node recovery time determined in vitro

Abstract

Evidence has indicated that the sarcoplasmic reticulum (SR) might be involved in the generation of spontaneous electrical activity in atrial pacemaker cells. We report the effect of disabling the SR with ryanodine (0.1 µM) on the sinus node recovery time (SNRT) measured in isolated right atria from 4-6-month-old male Wistar rats. Electrogram and isometric force were recorded at 36.5 o C. Two methods for sinus node resetting were used: a) pulse: a single stimulus pulse interpolated at coupling intervals of 50, 65 or 80% of the regular spontaneous cycle length (RCL), and b) train: a 2-min train of pulses at intervals of 50, 65 or 80% of RCL. Corrected SNRT (cSNRT) was calculated as the difference between SNRT (first spontaneous cycle length after stimulation interruption) and RCL. Ryanodine only slightly increased RCL (<10%), but decreased developed force by 90%. When the pulse method was used, cSNRT (~40 ms), which represents intranodal/atrial conduction time, was independent of the coupling interval and unaffected by ryanodine. However, cSNRT obtained by the train method was significantly higher for shorter intervals between pulses, indicating the occurrence of overdrive suppression. In this case, ryanodine prolonged cSNRT in a rate-dependent fashion, with a greater effect at shorter intervals. These results indicate that: a) a functional SR, albeit important for force development, does not seem to play a major role in atrial automaticity in the rat; b) disruption of cell Ca 2+ homeostasis by inhibition of SR function does not appear to affect conduction; however, it enhances overdrive-induced depression of sinusal automaticity. Correspondence

TBX18 overexpression enhances pacemaker function in a rat subsidiary atrial pacemaker model of sick sinus syndrome

“…It also suggested greater suppression was associated with higher intracellular Ca 2+ , increased K + conductance and increased hyperpolarization (Musso & Vassalle, 1982). cRT was affected in another study by ryanodine showing greater overdrive suppression in the context of 0.1 μM ryanodine and a reduction in sarcoplasmic reticular function (Bassani et al 1999). Ad-Tbx18 infection in our work did not induce any change in Na + channels, K + channels or NCX, which may offer an explanation for the lack of change in overdrive suppression.…”

“…cRT was affected in another study by ryanodine showing greater overdrive suppression in the context of 0.1 μM ryanodine and a reduction in sarcoplasmic reticular function (Bassani et al . ). Ad‐Tbx18 infection in our work did not induce any change in Na + channels, K + channels or NCX, which may offer an explanation for the lack of change in overdrive suppression.…”

Intracellular Ca2+ and pacemaking within the rabbit sinoatrial node: heterogeneity of role and control

“…8). Previous work on single SAN cells (Bassani et al 1997; Honjo et al 2003), isolated intact SAN preparations (Honjo et al 2003), and isolated right atria (Lipsius, 1989; Bassani et al 1999) has shown that ryanodine causes a modest slowing of pacemaking. Ryanodine at low (2 μmol l −1 ) or high concentrations (30 μmol l −1 ) does not cause cessation of spontaneous activity (Honjo et al 2003) nor does cyclopiazonic acid (Rigg & Terrar, 1996), thapsigargin (Bassani et al 1997), or, in some cases, application of caffeine (Fig.…”

Impact of waterborne and trophic mercury exposures on cardiac function of two ecologically distinct Neotropical freshwater fish Brycon amazonicus and Hoplias malabaricus

“…To evaluate the role of SR Ca 2+ stores in excitation-contraction coupling, the experiments described above were repeated after addition of the alkaloid ryanodine (10 M) to the bath 30 min before each protocol to inhibit SR function (Mill et al, 1998). Ryanodine promotes continuous leakage of the stored Ca 2+ in SR and disrupts SR Ca 2+ release by the Ca 2+ pool that enters the cardiomyocyte through sarcolemmal Ca 2+ channels (Bassani et al, 1999).…”