Influence of nitric oxide and vasoactive intestinal peptide on the spontaneous and triggered electrical and mechanical activities of the canine ileum.

Modulation of canine ileal pacemaker activity by nitric oxide (NO) or vasoactive intestinal peptide (VIP) was studied during recording of the intracellular electrical and mechanical activity from the entire muscularis externa and from an isolated circular muscle preparation both cut in the long axis of the circular muscle. In the whole-thickness preparation with cholinergic and adrenergic nerve function blocked, the inhibitory junction potentials (IJPs) recorded near the myenteric plexus (MyP) or deep muscular plexus (DMP) were abolished by omega-conotoxin GVIA (omega-CTX, 10(-7) to 3 x 10(-7) M), tetrodotoxin (TTX, 1 microM), or the NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NNA at 50 microM). IJPs from electrical field stimulation triggered slow waves (TSWs); after TTX or omega-CTX, TSWs still occurred, advanced in time and increased in amplitude after TTX. Addition of L-NNA advanced the onset of the TSWs after omega-CTX. TTX, L-NNA, or omega-CTX left the resting membrane potentials, the characteristics of spontaneous slow waves, or TSWs evoked by a long stimulating pulse unchanged. L-NNA at 100 microM enhanced the amplitude but not the frequency of spontaneous slow waves. TTX and NOS blockers all increased circular muscle contractions associated with the spontaneous slow waves and TSWs. In isolated circular muscle preparations, the NOS inhibitors N omega-nitro-L-arginine methyl ester (L-NAME at 300 microM) or L-NNA at 100 microM abolished the IJPs and increased the regularity and amplitude of spontaneous slow waves and associated contractions, but TSWs could not be evoked before or after NOS inhibition. The NO donor 3-morpholinosydnonimine hydrochloride (SIN-1) at 200 microM caused hyperpolarizations (10-15 mV) similar to the IJP mediator, attenuated the IJPs, and abolished mechanical activities. SIN-1 increased the slow wave frequency but decreased the amplitude and duration of spontaneous slow waves and TSWs. VIP (10(-6) M) decreased contraction and slow wave amplitude and prolonged IJP duration without affecting membrane potential or slow wave frequency. We conclude that spontaneous slow waves and TSWs originate independently of neural activity. Pacemaking regions possess inhibitory neural inputs that release NO to mediate IJPs and relaxation and influence the delay before a TSW. NO (not VIP) release from nerves inhibits initiation of spontaneous slow waves or TSWs near the MyP, and spontaneous NO release modulates pacemaking activity from the DMP.

Ca2+ role in myogenic and neurogenic activities of canine ileum circular muscle.

The role of Ca2+ in myogenic and neural activation in canine ileum circular muscle (CM) was studied during simultaneous recordings of contractile and electrical activity in cross-sectioned slabs of muscularis externa or of isolated CM with deep muscular plexus (DMP) intact. Ca(2+)-free Krebs solution abolished inhibitory junction potentials (IJP) and contractions before changes in CM membrane potentials and while slow waves (SW) persisted at lower amplitude and frequency. This medium abolished SW more rapidly in isolated CM than in intact muscle strips and affected triggered SW (TSW) by 100-ms pulses recorded near myenteric plexus or near DMP differentially in the full-thickness preparation; TSW did not occur in isolated CM. Ni2+, a nonselective Ca2+ channel antagonist, left IJP unchanged and reduced contractions, frequencies, and amplitudes of spontaneous SW and TSW, but increased their durations. Nifedipine abolished contractions but SW, TSW, and IJP were unaffected. Cyclopiazonic acid (CPA) increased SW frequency, produced spikes on SW plateaus, and increased CM tone, but did not affect IJP or resting membrane potentials. In nifedipine-pretreated strips, CPA decreased SW frequencies and amplitudes, evoked less tone, depolarized membrane potentials, and left IJP unaltered. The neuronal N-type Ca2+ channel blocker omega-conotoxin GVIA abolished IJP, without affecting SW or TSW. We conclude that Ca2+ influx, not through L- or N-type Ca2+ channels, helps initiate ileal SW; L-type Ca2+ channels provide Ca2+ for contraction and N-type Ca2+ channels provide Ca2+ for IJP mediator release. Frequencies of SW may be modulated by uptake of Ca2+ into pacemaker stores.

Agonist and antagonist activity during voluntary upper-limb movement in patients with stroke.

Forty-four patients with hemiplegia following stroke and 10 nondisabled subjects were studied to examine the contributions inadequate motor unit recruitment and co-contraction attributable to impaired antagonist inhibition play in the movement disorder of the hemiplegic arm. Electromyographic data were recorded from agonist and antagonist muscles while subjects attempted six specified tasks. Data from subjects who could complete the tasks were compared with those who could not complete the tasks. Differences between the two groups were found in the electromyographic data obtained from the agonist muscles. Electromyographic values were consistently and significantly lower in patients who were unable to complete the tasks than in patients who were able to complete the tasks. In the antagonist muscles, a significant difference was noted only once; in this case, the EMG values were again lower in the group of patients who were unable to complete the task. Inadequate recruitment of agonists, not increased activity in the antagonists, was a consistent finding in patients who were unable to carry out the movement tasks. This study theoretically supports aiming treatment efforts at improving motoneuron recruitment rather than reducing activity in antagonists while retraining arm function.

Effects of chronic cerebellar stimulation (CCS) setting on the gait and speech of a spastic cerebral palsy adult.

A single (N = 1) spastic cerebral palsy adult who had experienced Chronic Cerebellar Stimulation (CCS) for 9 years without any change in the stimulator settings was assessed at six different stimulator settings. These voltage settings varied from 0 volts to 40 volts and frequencies of stimulation from 0 to 200 Hz. Stimulation was with bipolar rectangular pulses with less than 0.2 C/mm2 charge per phase. Responses measured at each setting were quantitative gait, speech, and somatosensory evoked potential measurements. Additional clinical assessments were done by a neurologist and speech therapist. Alteration in stimulator settings occurred 1 week apart to allow for stabilization and all assessments were completed in the same sequence each day. None of the individual stimulator settings were known to any of the assessors or to the patient. The results showed consistently that the patient's gait and speech were poorest when the stimulator was switched off completely. Switching on the stimulator caused improved function according to all assessments. There was consistent improvement in gait and speech when the rate of the cerebellar stimuli was high (for voltages between 0 and 40 V). Changing the voltage (within the range 0 to 40 V), while keeping the frequency of stimulation constant, did not appear to have as much effect. This preliminary evaluation suggests that the technique of CCS is safe and can improve function in a measurable manner.