Deactivation kinetics of different components of calcium inward current in the membrane of mice sensory neurones.

Abstract

1. Deactivation kinetics of different components of calcium inward current were analysed by measuring 'tail currents' in intracellularly perfused sensory neurones isolated from dorsal root ganglia of newborn mice. 2. Deactivation of a low-threshold inactivating component had a mono-exponential time course with time constants that decreased as the potential was made more negative, and reached a limiting value of 1.0-1.2 ms at extreme hyperpolarizations. Replacement of Ca2+ by Ba2+ as a charge carrier decreased this value almost twofold. 3. Deactivation of the high-threshold component of calcium current contained two exponential components with time constants of similar potential dependence. The fast time constant became practically constant (0.1-1.2 ms) during repolarizations beyond -50 mV, and the slow time constant became constant (0.80-0.85 ms) at repolarization beyond -70 mV. 4. Replacement of intracellular aspartate with phosphate, or a depolarized holding potential of -40 mV, abolished reversibly the slow component of the tail current; in parallel, the peak current-voltage relation of the current became shifted by 15-20 mV in the depolarizing direction. 5. Extracellular application of the calcium channel agonist Bay K 8644 (2.5-5 mumol/l) did not change deactivation kinetics of the low-threshold current; however, it increased considerably the slow exponential component of high-threshold current deactivation or induced such a component in conditions when the latter was absent before application (Vh = -40 mV; cell perfusion with Tris phosphate). 6. The data obtained are analysed on the basis of the presence of three types of calcium channels in the neuronal membrane which possess similar kinetic mechanisms of activation and deactivation but differ in the activation thresholds and the time constants of transitions between open and closed states. The three calcium channels differ also in interaction with different permeant ions and calcium channel agonists.