PubMed · 8560085
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T Similowski, J P Derenne. 1995. [Phrenic stimulation].. https://pubmed.ncbi.nlm.nih.gov/8560085/
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The spontaneously hypertensive rat model has been used to show that hypertension is an important pathophysiological risk factor in age-related hearing loss. In the present study, compound action potential (CAP), electrochemical potential (ECP), and potassium concentration (CK+) measurements were taken from the cochlea of genetically predisposed, spontaneously hypertensive rats (SHR) and from normotensive Wistar-Kyoto (WKY) rats. In the SHR model, as the duration of hypertension increased with the animal's age (from 3 to 8 months), CAP thresholds increased, ECP increased in marginal cells only, and CK+ increased in both endolymph and marginal cells. Collectively, the data suggest that ionic alternations of cellular potentials are involved in hearing changes in the hypertensive state. Ultimately, such data may assist in understanding hearing loss in individuals who are diagnosed with hypertension.
BACKGROUND: The class III antiarrhythmic agent RP 58866 and its active enantiomer, terikalant, are reported to selectively block the inward rectifier K+ current, IK1. These drugs have demonstrated efficacy in animal models of cardiac arrhythmias, suggesting that block of IK1 may be a useful antiarrhythmic mechanism. The symmetrical action potential (AP)-prolonging and bradycardic effects of these drugs, however, are inconsistent with a sole effect on IK1. METHODS AND RESULTS: We studied the effects of RP 58866 and terikalant on AP and outward K+ currents in guinea pig ventricular myocytes. RP 58866 and terikalant potently blocked the rapidly activating delayed rectifier K+ current, IKr, with IC50S of 22 and 31 nmol/L, respectively. Block of IK1 was approximately 250-fold less potent; IC50S were 8 and 6 mumol/L, respectively. No significant block of the slowly activating delayed rectifier, IK1, was observed at < or = 10 mumol/L. The phenotypical IKr currents in mouse AT-1 cells and Xenopus oocytes expressing HERG were also blocked 50% by 200 to 250 nmol/L RP 58866 or terikalant, providing further conclusive evidence for potent block of IKr. RP 58866 < or = 1 mumol/L and dofetilide increased AP duration symmetrically, consistent with selective block of IKr. Only higher concentrations (> or = 10 mumol/L) of RP 58866 slowed the rate of AP repolarization and decreased resting membrane potential, consistent with an additional but substantially less potent block of IK1. CONCLUSIONS: These data demonstrate that RP 58866 and terikalant are potent blockers of IKr and prompt a reinterpretation of previous studies that assumed specific block of IK1 by these drugs.
To document synaptic interactions between neurons in the precentral cortex of macaque monkeys, we recorded in vivo the intracellular (IC) membrane potentials of cortical neurons simultaneously with extracellular (EC) action potentials of neighboring cells. The synaptic potentials correlated with EC spikes were obtained by spike-triggered averages (STA) of the IC membrane potentials for 373 cell pairs recorded in anesthetized and awake behaving monkeys. Sixty-three STAs (17%) showed excitatory postsynaptic potentials (EPSPs), beginning after the trigger spike. Pure EPSPs had onset latencies of 0.9 +/- 0.7 msec (mean +/- SD) and amplitudes of 226 +/- 130 microV. Sixteen STAs (4%) showed postspike inhibitory postsynaptic potentials (IPSPs), with onset latencies of 0.4 +/- 0.4 msec and amplitudes of -274 +/- 188 microV. The most common waveform, observed in 82% of the STAs with features, was a broad depolarization straddling the trigger spikes, reflecting synchronized synaptic input to both IC and EC neurons. These average synchronous excitation potentials (ASEPs) began 14.3 +/- 6.6 msec before the trigger spike and had amplitudes of 1064 +/- 867 microV. Twenty-three STAs (6%) showed an average synchronous inhibitory potential (ASIP): a hyperpolarization beginning before the trigger spike and reflecting IPSPs produced by a group of local inhibitory cells synchronized with the trigger cell. ASIPs had an onset latency of -5.5 +/- 2.7 msec and amplitude of -589 +/- 502 microV. Combinations of synchronous and postspike potentials were also observed. Successive recordings provided examples of convergent and divergent connections between EC and IC cells. Neuron pairs with depolarizing postsynaptic potentials (PSPs) in the STA yielded peaks in the cross-correlograms of the IC and EC action potentials; the peak area was proportional to the amplitude of the PSP. These data suggest that a significantly larger proportion of cortical neurons interact through synchronous activity than through simple serial interactions; moreover, synchronous excitation affected more widely separated cell pairs than EPSPs and IPSPs, which were seen most often among the closest cells.