Biomedical subjects

Craig B Neylon

Publications and source records attributed to Craig B Neylon.

3 recordsLinked to original sources

PubMed2003

Oligophrenin-1, a Rho GTPase-activating protein (RhoGAP) involved in X-linked mental retardation, is expressed in the enteric nervous system.

Oligophrenin-1 is a RhoGTPase-activating protein (RhoGAP) that is involved in the regulation of shape changes in dendritic spines, and outgrowth of axons and dendrites in the brain. These changes in neuronal morphology are central to the mechanisms of plasticity, learning, and memory. Although the enteric nervous system also exhibits long-term changes in neuronal function, the expression and involvement of oligophrenin-1 has not previously been investigated. We show by RT-PCR analysis that oligophrenin-1 mRNA is expressed in the myenteric plexus (MP) of the guinea pig ileum. Sequencing of RT-PCR products showed that guinea pig oligophrenin-1 mRNA is 98% and 87% homologous to human and mouse oligophrenin-1, respectively, except that a 42 bp sequence is absent from the guinea pig mRNA. This 42 bp sequence codes for a sequence of 14 amino acids located near the carboxy-terminal end of the RhoGAP domain in the human sequence. An antibody that recognizes human oligophrenin-1 identified a 91 kDa protein band in rat and mouse brain lysates and in guinea pig sciatic nerve, and a 36 kDa protein band in both purified enteric ganglion cell and brain lysate from guinea pig. Oligophrenin-1 is localized specifically to neurons and varicose axons in the MPs and submucosal plexuses (SMPs) of the guinea pig and rat, but is not detectable in glial cells, smooth muscle, or other cell types. These findings indicate that oligophrenin-1 is expressed in the enteric nervous system, where it may regulate morphological changes in axons and dendrites, and thus modulate neuronal connectivity.

Animals↗

PubMed2002

Potassium channels and vascular proliferation.

Potassium channels are currently the focus of much attention because of their recently discovered role in the regulation of vascular smooth muscle growth. Dramatic alterations in the expression and activity of K+ channels causing marked changes in the cell's electrical properties accompany enhanced growth of smooth muscle cells (SMCs). These findings indicate that alterations in K+ channel function are important for SMC proliferation. However, the mechanisms by which changes in K+ channel activity influence cellular growth pathways are poorly understood. The emergent electrical properties caused by modulation of K+ channels are associated with marked differences in the spatial and temporal organization of Ca2+ signaling. Thus, changes in K+ channel function may represent a universal mechanism by which Ca2+ signals are targeted towards activation of gene expression and cell growth. As enhanced growth of smooth muscle underlies many cardiovascular diseases and clinical pathologies, the identification of an important role for K+ channels in SMC proliferation indicates a new source of therapeutic targets to regulate proliferative vascular disorders.

Animals↗

PubMed2002

Regulation of K+ channels underlying the slow afterhyperpolarization in enteric afterhyperpolarization-generating myenteric neurons: role of calcium and phosphorylation.

1. Myenteric afterhyperpolarization-generating myenteric (AH) neurons serve as intrinsic primary afferent neurons of the enteric nervous system and generate prolonged or slow afterhyperpolarizing potentials (slow AHP). The slow AHP is generated by an increase in a Ca2+-activated K+ conductance (gK-Ca) and is inhibited by enteric neurotransmitters leading to increased excitability. 2. Using cell-attached patch-clamp recordings from AH neurons, we have shown that K+ channels with an intermediate unitary conductance (IK channels) open following action potential firing. 3. In excised patches from AH neurons, we have identified an IK-like channel that can be activated by submicromolar levels of cytoplasmic Ca2+ and is not voltage dependent. 4. Application of the catalytic subunit of cAMP-dependent protein kinase to the cytoplasmic surface of inside-out patches inhibits the opening of IK-like channels previously activated by Ca2+. 5. The IK-like channels are resistant to external tetraethylammonium (5 mmol/L) and apamin (0.3-1 micro mol/L), but are inhibited by clotrimazole (10 micro mol/L). 6. Our present data support the idea that an increase in the open probability of IK-like channels in AH neurons following an increase in cytoplasmic [Ca2+] is responsible for the slow AHP and their opening is modulated by kinases.

Action Potentials↗