Two kinetically distinct components of hyperpolarization-activated current in rat superior colliculus-projecting neurons.

1. Whole-cell and perforated patch recording techniques were used to examine the activation, deactivation and inactivation of the time-dependent hyperpolarization-activated inward currents (Ih) in isolated superior colliculus-projecting (SCP) neurons from rat primary visual cortex. 2. Examination of inward current waveforms revealed the presence of two kinetically distinct components of Ih: one that activates with a time constant of the order of hundreds of milliseconds, and one that activates with a time constant of the order of seconds. We have termed these Ih,f and Ih,s, to denote the fast and slow components, respectively, of current activation. The time constants of activation of both Ih,f and Ih,s decrease with increasing membrane hyperpolarization. 3. Following the onset of hyperpolarizing voltage steps, a delay is evident prior to time-dependent inward current activation. This delay is voltage dependent and decreases with increasing membrane hyperpolarization. 4. The sigmoidal inward current waveforms are well fitted by the sum of two exponentials in which the faster term, corresponding to the activation of Ih,f, is raised to the power 1.34 +/- 0.26 (mean +/- S.D.). The non-integral exponent suggests that Ih,f activation involves at least two energetically non-equivalent gating transitions prior to channel opening. 5. Over a limited voltage range, tail currents could also be resolved into two distinct components. The faster component, which corresponds to the deactivation of Ih,f, decayed over a single exponential time course with a mean (+/- S.D.) time constant of 355 +/- 161 ms at -70 mV. Ih,s decay also followed a single exponential time course with a mean (+/- S.D.) time constant of 2428 +/- 1285 ms at -70 mV. Both deactivation time constants decreased with increasing depolarization. 6. The separation of inward current activation and deactivation into two distinct components and the lack of correlation between the relative amplitudes of these components suggest that Ih,f and Ih,s reflect the presence of two functionally distinct channel populations. 7. No decrements in time-dependent hyperpolarization-activated inward currents were observed during hyperpolarizations lasting up to 18 s, suggesting that neither Ih,f nor Ih,s inactivates from the open state. In addition, 10 s depolarizations to 0 mV prior to activation did not alter the waveforms of the inward currents activated directly from -40 mV, suggesting that Ih,f and Ih,s also do not inactivate from closed states. 8. The hyperpolarization-activated currents in rat SCP neurons are ideally suited to contribute to the control of the resting membrane potential and input resistance.(ABSTRACT TRUNCATED AT 400 WORDS)