Figure 8. Onset of DHP-induced inactivation is voltage-dependent and recovery is modulated by inactivation determinants.

Figure 8

Onset of DHP-induced inactivation is voltage-dependent and recovery is modulated by inactivation determinants. A) (+)Isradipine (1μM) accelerates barium current decay through L-type construct Cav1.2(β1a) (traces on the left) and slows recovery from inactivation/block (right panel) about 4,5-fold (τrecovery,control = 0.63 s vs. τrecovery, isradipine = 2.85 s). B) Amino acid residue I1471 is believed to form part of the DHP receptor. Substitution I1471A slows inactivation (fig. 4B). Traces in the left panel illustrate barium currents through I1471A in control and the presence of (+)isradipine (1 μM). The right panel illustrates faster recovery of mutant I1471A from inactivation at rest compared to Cav1.2(β1a) (compare with A). Recovery of I1471A in drug was faster than in Cav1.2 and not significantly different from control (τrecovery,control =0.50 s, τrecovery, isradipine = 0.46 s compare to A). Data from reference 34 with permission. C) Voltage-dependent acceleration of the barium current decay of slowly inactivating mutant V1477A by 1 μM (+)isradipine (inset). Voltage-dependencies of the time constant of fast Cav1.2(β1a) inactivation and the rate of (+)isradipine-induced current decay are illustrated. The time constant of current decay of V1477A in the absence of drug (open circles) ranged between 10 and 25 seconds. Data reproduced from reference 35 with permission.

From: Calcium Channel Block and Inactivation: Insights from Structure-Activity Studies

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