TABLE I.

Summary of kinetics

Step Probes Resting FRETr % ΔFRETr % DelayonτonDelayoffτoffEC50 (oxo-M) nM 
M1R activation M1R-YFP-CFP 0.88 +6  <0.1  0.18  
M1R/Gβ interaction M1R-CFP 0.42 ± 0.07 +33 ± 6  0.20 ± 0.03  3.7 ± 0.2 330 ± 150 
 1-YFP        
q/Gβ1 separation q-CFP 0.15 ± 0.01 −10  2.0 5.8 35  
 1-YFP (with GRK2) 0.26 ± 0.03 −17 ± 2 0.14 ± 0.05 2.8 ± 0.3 9.9 ± 2.9 28 ± 2 160 ± 100 
q/PLCβ1 interaction q-CFP 0.14 ± 0.03 +20 ± 2 0.38 ± 0.25 1.3 ± 0.3 0.34 ± 0.14 3.6 ± 0.5 260 ± 190 
 PLCβ1-YFP        
PIP2 hydrolysis PH(PLCδ1)-CFP 0.14 ± 0.03 −44 ± 3 1.3 ± 0.2 5.4 ± 1.6 29 ± 2 59 ± 7 28 ± 14 
 PH(PLCδ1)-YFP        
Kv7.2/7.3 closure M current   1.4 ± 0.3 5.0 ± 0.6 34 ± 6 123 ± 20 120 ± 100 
Kv7.2/7.3 closure with PLCβ M current   0.78 ± 0.07 1.2 ± 0.1 11 ± 7 62 ± 22  
 PLCβ1-YFP        
Kv7.2/7.3 closure with PH probes M current   2.1 ± 0.1 5.7 ± 0.7 11 ± 5 63 ± 9  
 PH(PLCδ1)-CFP        
 PH(PLCδ1)-YFP        
Step Probes Resting FRETr % ΔFRETr % DelayonτonDelayoffτoffEC50 (oxo-M) nM 
M1R activation M1R-YFP-CFP 0.88 +6  <0.1  0.18  
M1R/Gβ interaction M1R-CFP 0.42 ± 0.07 +33 ± 6  0.20 ± 0.03  3.7 ± 0.2 330 ± 150 
 1-YFP        
q/Gβ1 separation q-CFP 0.15 ± 0.01 −10  2.0 5.8 35  
 1-YFP (with GRK2) 0.26 ± 0.03 −17 ± 2 0.14 ± 0.05 2.8 ± 0.3 9.9 ± 2.9 28 ± 2 160 ± 100 
q/PLCβ1 interaction q-CFP 0.14 ± 0.03 +20 ± 2 0.38 ± 0.25 1.3 ± 0.3 0.34 ± 0.14 3.6 ± 0.5 260 ± 190 
 PLCβ1-YFP        
PIP2 hydrolysis PH(PLCδ1)-CFP 0.14 ± 0.03 −44 ± 3 1.3 ± 0.2 5.4 ± 1.6 29 ± 2 59 ± 7 28 ± 14 
 PH(PLCδ1)-YFP        
Kv7.2/7.3 closure M current   1.4 ± 0.3 5.0 ± 0.6 34 ± 6 123 ± 20 120 ± 100 
Kv7.2/7.3 closure with PLCβ M current   0.78 ± 0.07 1.2 ± 0.1 11 ± 7 62 ± 22  
 PLCβ1-YFP        
Kv7.2/7.3 closure with PH probes M current   2.1 ± 0.1 5.7 ± 0.7 11 ± 5 63 ± 9  
 PH(PLCδ1)-CFP        
 PH(PLCδ1)-YFP        

For each kinetic step, the probes used, average resting FRETr ratio, percent change, delays, and single-exponential time constants from onset and washout of 10 µM oxo-M are given. The reported EC50 is based on a Hill fit to steady-state responses.

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