Table 1.

Kinetic modeling of PS effects on GABA_Areceptors

Parameter	Peak response	Fast component (msec)	Slow component (msec)	% Fast
Deactivation (5 msec application)
Control	0.74	11.8	125	50
↑d2	0.52	7.6	200	64
↓r2	0.74	14.9	217	79
↓β2	0.47	7.4	91	69
↑α2	0.60	5.4	91	76
↑k_off	0.74	11.2	53	65
↓k_on	0.73	11.6	123	48
↑d1 + ↑d2	0.52	7.6	200	64
Desensitization (200 msec application)
Control	0.74 → 040	12.0	47.6	92
↑d2	0.52 → 0.19	7.7	19.6	97
↓r2	0.74 → 0.19	16.9	—	—
↓β2	0.47 → 0.17	7.5	47.6	97
↑α2	0.60 → 0.17	5.6	43.4	98
↑k_off	0.74 → 0.38	11.9	129.8	83
↓k_on	0.73 → 0.38	12.0	120.5	83
↑d1 + ↑d2	0.52 → 0.19	7.7	43.4	94
β-Alanine deactivation (5 msec application)
Control	0.25	5.6
↑d2	0.21	6.3
↓r2	0.25	5.3
↓β2	0.12	4.0
↑α2	0.14	3.0
↑d1 + ↑d2	0.20	6.3

Parameters for control simulations were derived from Mozrzymas et al. (1999) and Jones et al. (1998), adjusting the rate between d1 and d2 to maintain microscopic reversibility (Fig. 8). The Parameter column presents control simulations and simulations using 3× changes in the rate constants. Peak responses represent the peak open channel probability. The deactivation data represent the decay of responses to 1 mm GABA after a 5 msec simulated application. In desensitization simulations the peak response column represents peak → steady-state responses during a 200 msec simulated 1 mmGABA application. The values underlined in the table represent effects that differed qualitatively from the observed experimental actions of PS. The effects of β-alanine were modeled by decreasing k_on and increasing k_off, as described in Jones and Westbrook (1995) and Jones et al. (1998).