Protein kinase C inhibition blocks the early appearance of vestibular compensation

This study tests the hypothesis that activation of protein kinase C (PKC) i s a critical step for early recovery from spontaneous nystagmus after unila teral ablation of the vestibular periphery. Halothane-NO2-O-2-anesthetized Long-Evans rats received a 5-mu l intracerebroventricular bolus of vehicle (distilled water, six rats), PKC inhibitor [Iso-H-7 (10 mM, four rats; 50 m M, five rats) or bisindolemaleimide I(Bis-I, 10 mu M, six rats)], PKG and P KA inhibitor (A-3, 1 mM, six rats), or the serine-threonine protein kinase inhibitor H-7 (1 mM, five rats; 10 mM, five rats). Surgical unilateral laby rinthectomy (UL) was completed within 15 min. Sham control groups showed no nystagmus. Bis-I and Iso-H-7 significantly retarded the disappearance of s pontaneous nystagmus quick phases for 8 h after UL (p < 0.05). The effects of Iso-H-7 were dose-dependent: more nystagmus quick phases (p < 0.05) were present in the 50 mM than the 10 mM group at 7 and 8 h post-UL. The rats g iven A-3 showed a delayed retardation of nystagmus loss, which differed sig nificantly (p < 0.05) from controls at 4-8 h after labyrinthectomy. The num ber of nystagmus quick phases was significantly greater than controls (p < 0.05) in the 10 mM H-7 group at 4, 5, 6 and 48 h post-UL, but only at 6 and 24 h post-UL in the 1 mM H-7 group. Thus, PKC activation is an important e arly requirement for vestibular compensation during the acute post-labyrint hectomy period, while cyclic-nucleotide dependent kinases may be important in a later time frame. (C) 1999 Elsevier Science B.V. All rights reserved.