Slowed inactivation at positive potentials in a rat axonal K+ channel is not due to preferential closed-state inactivation.

We have investigated slow inactivation in a rat axonal K+ channel, the I channel. Using voltage steps to potentials between -70 mV and +80 mV, from a holding potential of -100 mV, we observed a marked slowing of inactivation at positive potentials: the time constant was 4.5+/-0.4 s at -40 mV (mean +/- S.E.M.), increasing to 14.7+/-2.0 s at +40 mV. Slowed inactivation at positive potentials is not consistent with published descriptions of C-type inactivation, but can be explained by models in which inactivation is preferentially from closed states (which have been developed for Kv2.1 and some Ca2+ channels). We tested two predictions of preferential closed-state models: inactivation should be more rapid during a train of brief pulses than during a long pulse to the same potential, and the cumulative inactivation measured with paired pulses should be greater than the inactivation at the same time during a continuous pulse. The I channel does not behave according to these predictions, indicating that preferential closed-state inactivation does not explain the slowing of inactivation we observe at positive potentials. Inactivation of the I channel therefore differs both from C-type inactivation, as presently understood, and from the inactivation of Kv2.1.

Saddle block with pethidine for perineal operations.

Saddle blockade with pethidine hydrochloride was performed in 111 patients undergoing short surgical operations on the perineum. A dose of 5% pethidine 0.5 mg kg-1 was injected to the subarachnoid space at L4-5 or L5-S1 with the patient in the sitting position. Sensory blockade was achieved in 5.28 +/- 1.43 min. This extended to the sacrococcygeal area, perineum, buttocks and posterior surface of thighs, and was followed 1-2 min later by motor blockade. During the operation the patients were stable haemodynamically and no respiratory depression was recorded. Sensory blockade lasted for 141 +/- 26.06 min and was followed by postoperative analgesia, the mean duration of which was 301 +/- 98.38 min. Postoperative neurological complications were recorded in three patients (2.7%): headache alone in one, headache associated with backache in one, and leg weakness, backache, nuchal rigidity and photophobia in another. Seven patients (6.3%) complained of itching, five patients (4.5%) of nausea and vomiting and two (1.8%) developed urinary retention.