![Figure 7. Simulated stimulation of RyR and IP3R. (A) The combined effect of caffeine (see Materials and methods) and IP3R block was simulated during simulation of spontaneous activity. (B) The combined effect of IP3-AM increasing the [IP3] slowly (see Materials and methods) and RyR block was simulated during simulation of spontaneous activity. For A and B, the near-SL and near-SR cytosolic [Ca2+] are shown. (C) The steady-state spontaneous AP frequency versus [IP3] (circles) with a sigmoidal fit to the data (solid line). When increasing [IP3] to values of 0.08 μM and above, arrhythmias were observed increasingly. (D) The experimentally recorded distribution of the frequencies of the spontaneous activity in E9-E11 mouse cardiomyocytes (n = 94). The raw data are from Rapila et al. (2008).](https://cdn.rupress.org/rup/content_public/journal/jgp/132/4/10.1085_jgp.200809961/7/jgp_200809961_rgb_fig7.jpeg?Expires=1767733046&Signature=Yrj48Iq2jRbUPOncBrV-pSelMUDLjNdmEgnDR80MBGnFeRT~Er~b91xuFo0yyHGF5EXXpD5UPsm7U4WtUmoTnAjWKiNodwwMH1o4KFnH0l3Pj-1~qe1WU~Rg-xw04v1PxUS10G5vuiUm3vLKwqdXRcbUO3TRYNk88iDjhrOWHhUbbKbt~5wd4U2hEZvJ7QMqpYaeFlPMBawcVSPMZ9l5NoqljJODNsUsfoJVsq0xueEQuzWKMMnhqsWYLXZuzOLRejIGPbJevXuBvGcDenijggd4FzcmSwCyiWy0~DYNVvHkmXyELBYb0Mh5bMxJrv5AC1bMEof1R3M37uWQIH3LeA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Simulated stimulation of RyR and IP3R. (A) The combined effect of caffeine (see Materials and methods) and IP3R block was simulated during simulation of spontaneous activity. (B) The combined effect of IP3-AM increasing the [IP3] slowly (see Materials and methods) and RyR block was simulated during simulation of spontaneous activity. For A and B, the near-SL and near-SR cytosolic [Ca2+] are shown. (C) The steady-state spontaneous AP frequency versus [IP3] (circles) with a sigmoidal fit to the data (solid line). When increasing [IP3] to values of 0.08 μM and above, arrhythmias were observed increasingly. (D) The experimentally recorded distribution of the frequencies of the spontaneous activity in E9-E11 mouse cardiomyocytes (n = 94). The raw data are from Rapila et al. (2008).
