Regulation of neuronal nitric oxide synthase through alternative transcripts.

Nitric oxide (NO) participates in diverse physiological processes ranging from neurotransmission to muscle relaxation. Neuronal-derived NO can be either beneficial or detrimental depending on the cellular context. Neuronal NO synthase (nNOS) must therefore be tightly regulated.

Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy.

Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntrophin but not with other proteins in the dystrophin complex analyzed.

Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle.

Nitric oxide (NO) functions as a molecular mediator in numerous processes in cellular development and physiology. Differential expression and regulation of a family of three NO synthase (NOS) gene products help achieve this diversity of action. Previous studies identify post-translational modification and interaction of NOS with specific protein targets as tissue-specific modes of regulation.

Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy.

Nitric oxide (NO) is synthesized in skeletal muscle by neuronal-type NO synthase (nNOS), which is localized to sarcolemma of fast-twitch fibers. Synthesis of NO in active muscle opposes contractile force. We show that nNOS partitions with skeletal muscle membranes owing to association of nNOS with dystrophin, the protein mutated in Duchenne muscular dystrophy (DMD).

Chloride currents in freshly isolated rat retinal pigment epithelial cells.

Cells of the retinal pigment epithelium (RPE) were isolated from neonatal rats. The perforated-patch clamp technique, using amphotericin-B, revealed a chloride current, which was detected as a 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive component. A variety of chloride-channel inhibitors, other than DIDS, also blocked the chloride current, including 9-anthracenecarboxylic acid (9-AC), niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and N-phenylanthranilic acid (DPC).