The aim of this study was to test the hypothesis that the cells in the brain stem pedunculopontine tegmentum (PPT) are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. To test this hypothesis, one of four different doses of the excitatory amino acid L-glutamate (15, 30, 60, and 90 ng) or saline (control vehicle) was microinjected unilaterally into ...

Work in heterologous systems has revealed that members of the Rad, Rem, Rem2, Gem/Kir (RGK) family of small GTP-binding proteins profoundly inhibit L-type Ca(2+) channels via three mechanisms: 1), reduction of membrane expression; 2), immobilization of the voltage-sensors; and 3), reduction of Po without impaired voltage-sensor movement. However, the question of which mode is the critical one f...

RATIONALE In heart, Ca(2+) entering myocytes via Ca(V)1.2 channels controls essential functions, including excitation-contraction coupling, action potential duration, and gene expression. RGK GTPases (Rad/Rem/Rem2/Gem/Kir sub-family of Ras-like GTPases) potently inhibit Ca(V)1.2 channels, an effect that may figure prominently in cardiac Ca(2+) homeostasis under physiological and disease conditi...

Crump, Shawn M., Robert N. Correll, Elizabeth A. Schroder, William C. Lester, Brian S. Finlin, Douglas A. Andres, and Jonathan Satin. L-type calcium channel -subunit and protein kinase inhibitors modulate Rem-mediated regulation of current. Am J Physiol Heart Circ Physiol 291: H1959–H1971, 2006. First published April 28, 2006; doi:10.1152/ajpheart.00956.2005.—Cardiac voltage-gated L-type Ca cha...

Considerable evidence suggests that brain stem pedunculopontine tegmentum (PPT) cholinergic cells are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. However, much of this evidence comes from indirect studies. Thus, although involvement of PPT cholinergic neurons has been suggested by numerous investigations, the excitation of PPT cholinergic neur...

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep depri...

Recently, it was hypothesized that acute or cumulative suppression of non-REM sleep intensity might be related to the therapeutic effects of antidepressants. This intensity has been proposed to be expressed in the EEG power density in non-REM sleep. In the present study, the relationship was examined between the changes of EEG power density in non-REM sleep and the changes in clinical state in ...

Cardiac voltage-gated L-type Ca channels (Ca(V)) are multiprotein complexes, including accessory subunits such as Ca(V)beta2 that increase current expression. Recently, members of the Rad and Gem/Kir-related family of small GTPases have been shown to decrease current, although the mechanism remains poorly defined. In this study, we evaluated the contribution of the L-type Ca channel alpha-subun...

Rem, Rem2, Rad, and Gem/Kir (RGK) represent a distinct GTPase family with largely unknown physiological functions. We report here that both Rem and Rad bind directly to Ca2+ channel beta-subunits (CaV beta) in vivo. No calcium currents are recorded from human embryonic kidney 293 cells coexpressing the L type Ca2+ channel subunits CaV1.2, CaV beta 2a, and Rem or Rad, but CaV1.2 and CaV beta 2a ...

The amygdala has emerged as an important forebrain modulator of arousal. Acetylcholine plays a role in the regulation of sleep and wakefulness, particularly rapid eye movement sleep (REM). The major cholinergic input to the amygdala comes from the basal forebrain, a region primarily linked to wakefulness. We examined sleep and the encephalogram for 8 h following bilateral microinjections into t...