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T M Moriarty

Publications and source records attributed to T M Moriarty.

21 records · Page 2Linked to original sources

Beta gamma subunits of GTP-binding proteins inhibit muscarinic receptor stimulation of phospholipase C.

This study examines the mechanism of guanine nucleotide-binding protein (G protein) coupling of receptors to phospholipase C. The Xenopus oocyte has a muscarinic receptor-activated Cl- current that is mediated by inositol 1,4,5-trisphosphate. Modulation of the muscarinic receptor-evoked Cl- current was examined under voltage clamp in oocytes injected with resolved G-protein subunits. The presence of an alpha subunit of G proteins in oocytes was shown by pertussis toxin-labeling of a 41-kDa band in oocyte membranes. The presence of the beta subunit of G proteins was demonstrated by immunoblotting experiments with an antiserum (U-49) that is specific for the beta subunit. Pertussis toxin treatment of oocytes resulted in the uncoupling of muscarinic receptors from activation of the Cl- current. Cells microinjected with 1.5 ng of human erythrocyte beta gamma-subunit complex or 1.0 ng of bovine brain beta gamma-subunit complex showed approximately a 95% reduction in the evoked Cl- current. Cells injected with equal volumes of protein storage vehicle showed no change in response. Cells injected with boiled beta gamma subunits, bovine serum albumin, or resolved alpha subunits also showed no reduction in response. Cells injected with various concentrations of beta gamma subunits showed a concentration dependence with half-maximal inhibition of the muscarinic activated Cl- current at about 10 nM. Cells injected with 1.0 ng of bovine brain beta gamma subunits could not respond to bath-applied agonist but could generate the Cl- current on intracellular injection of inositol 1,4,5-trisphosphate. These observations suggest that there is a G protein responsible for muscarinic receptor-mediated signal transduction through phospholipase C and that it is an alpha beta gamma heterotrimer. It appears that the mode of action of the G protein in the phospholipase C system may be similar to that of the hormone-activated adenylyl cyclase.

Animals↗

Effects of whole-body rotation on masseteric motoneuron excitability.

Vestibular stimulation is a popular clinical treatment for enhancing the excitability of spinal motoneurons innervating trunk and limb muscles, but whether vestibular stimulation can also influence trigeminal motoneurons is not known. We determined whether or not vestibular stimulation evoked by rotation of a seated subject would modify the excitability of masseteric motoneurons. The amplitude and frequency of occurrence of masseteric compound action potentials evoked by standard chin taps provided measures for assessing masseteric motoneuron excitability. Eleven healthy adults with no orofacial or otologic disorders served as subjects. Each sat in a motorized dental chair with his head stabilized by a halo head-piece so that chair rotation caused labyrinthine excitation. The frequency (3/s) of chin taps and their impact force were maintained constant by microcomputer control. After each tap, a 16-ms sample of EMG recorded from surface electrodes over the right masseter was digitized and stored for subsequent visual inspection. Only compound action potentials meeting rigorous criteria in terms of latency, amplitude, duration, and waveform were accepted as responses. The mean frequencies of occurrence and the mean amplitudes of the responses showed wide variability. Histogram displays of every response for each subject, however, revealed enhanced output from the masseteric motoneuron pool during the decleration and postrotation phases. In subjects not immediately retested this enhancement was persistent but decayed during the next 5 min. In five subjects the experiment was repeated after 1 min. The changes in response variables during phases 3 and 4 were significantly less than on the first trial, suggesting habituation. These results provide quantitative evidence that the dynamic input from vestibular ampullary receptors in response to rotation enhances masseteric motoneuron output.

Adult↗

Identification and assessment of factors contributing to variability of the jaw jerk.

Unlike limb monosynaptic reflexes, the jaw jerk reflex ( JJR ) is extremely variable. We studied 35 healthy adults to determine the relative contributions of extrinsic and intrinsic factors underlying this variability. Each subject sat in a dental chair with his head and chin securely stabilized. Chin taps, delivered by a solenoid-driven plunger, were quantified with a piezo -transducer. The reflex response was recorded from surface electrodes over the right masseter muscle. A nasal thermistor signalled phases of respiration. Five of the 35 subjects had no reflex when relaxed, but during 15 degrees neck extension or voluntary contraction of the platysma muscle, a JJR appeared. The amplitude of the reflex varied considerably from trial to trial in all but one subject. A small component of this variability was due to minute changes in tap force despite head and chin stabilization and stimulus uniformity. Mean amplitudes of the reflex tended to increase with increases in tap force, but variability was large indicating intrinsic fluctuations in motoneuron excitability. Voluntary contraction of the platysma muscle and 15 degrees neck extension reliably enhanced the reflex. The JJR showed negligible respiratory modulation during quiet breathing. The reflex's variability in and among subjects precludes the use of the JJR as an index of masseteric motoneuron excitability. Our findings suggest that branchial motoneurons innervating the masticatory muscles receive far more diverse and fluctuating inputs than do somatic motoneurons innervating limb muscles.

Adolescent↗