Abstract-We recently demonstrated a direct relationship between autoregulation-related changes in renal vascular resistance (RVR) and renal interstitial ATP concentrations. To assess the possible role for extracellular ATP in the regulation of tubuloglomerular feedback (TGF)-mediated autoregulatory adjustments in RVR, renal interstitial ATP concentrations were measured with microdialysis probes in anesthetized dogs at different renal arterial pressures (RAPs) within the autoregulatory range during augmented and diminished activity of the TGF mechanism. Stepwise reductions in RAP from ambient pressure (129Ϯ3 mm Hg) to 102Ϯ2 mm Hg (step 1) and 75Ϯ1 mm Hg (step 2) resulted in significant decreases in ATP concentrations from 9.0Ϯ0.8 to 6.3Ϯ0.6 nmol/L in step 1 and to 4.2Ϯ0.5 nmol/L in step 2. Changes in RVR were highly correlated with changes in ATP concentrations (rϭ0.86, PϽ0.001, nϭ12). Acetazolamide (100 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , nϭ6), which increases solute delivery to the macula densa, thus augmenting TGF activity, significantly decreased renal blood flow (RBF) by Ϫ16Ϯ2% and glomerular filtration rate (GFR) by Ϫ22Ϯ4% and increased ATP concentrations from 8.4Ϯ0.7 to 15.5Ϯ1.4 nmol/L. Although basal RBF and GFR levels were reduced by the acetazolamide infusion, autoregulation efficiency was maintained, and interstitial ATP concentrations were significantly decreased in response to reductions in RAP by Ϫ36Ϯ4% in step 1 and by Ϫ54Ϯ2% in step 2. The relationship between changes in RVR and interstitial ATP concentrations was preserved during acetazolamide treatment (rϭ0.80, PϽ0.01). Inhibition of the TGF mechanism by furosemide significantly increased RBF by 33Ϯ6% and GFR by 13Ϯ2% and decreased ATP concentrations from 8.9Ϯ1.4 to 5.0Ϯ0.8 nmol/L (nϭ6). Furosemide caused marked impairment of RBF and GFR autoregulatory efficiency (by Ϫ14Ϯ3% and Ϫ11Ϯ3% in step 1 and by Ϫ26Ϯ2% and Ϫ18Ϯ4% in step 2, respectively). In the furosemide-treated kidneys, interstitial ATP levels remained low and were not altered during reductions in RAP (4.7Ϯ0.7 nmol/L in step 1 and 4.7Ϯ0.8 nmol/L in step 2), and changes in RVR did not exhibit a correlation with changes in ATP concentrations (rϭ0.22, Pϭ0.30). These data support the hypothesis that extracellular ATP contributes to autoregulatory adjustments in RVR that are mediated by changes in activity of the TGF mechanism. Key Words: adenosine Ⅲ tubuloglomerular feedback Ⅲ kidneys Ⅲ acetazolamide Ⅲ furosemide T he tubuloglomerular feedback (TGF) mechanism and the myogenic mechanism are the main mechanisms responsible for renal autoregulatory responses, 1-3 which are caused by active adjustments of vascular smooth muscle tone, primarily in the afferent arterioles. [1][2][3][4][5] The findings that the blockade of TGF activity results in significant impairment of renal autoregulation-mediated adjustments in renal blood flow (RBF) 6,7 or afferent arteriolar diameter 2,4,5,8 indicate that the normally observed high autoregulatory efficiency is dependent on the integrity of the TGF mechanism.TGF-mediated a...

The dynamic activity of afferent arteriolar diameter (AAD) and blood flow (AABF) responses to a rapid step increase in renal arterial pressure (100-148 mmHg) was examined in the kidneys of normal Sprague-Dawley rats (n = 11) before [tubuloglomerular feedback (TGF)-intact] and after interruption of distal tubular flow (TGF-independent). Utilizing the in vitro blood-perfused juxtamedullary nephron preparation, fluctuations in AAD and erythrocyte velocity were sampled by using analog-to-digital computerized conversion, video microscopy, image shearing, and fast-frame, slow-frame techniques. These assessments enabled dynamic characterization of the autonomous actions and collective interactions between the myogenic and TGF mechanisms at the level of the afferent arteriole. The TGF-intact and TGF-independent systems exhibited common initial (0-24 vs. 0-13 s, respectively) response slope kinetics (-0.53 vs. -0.47% DeltaAAD/s; respectively) yet different maximum vasoconstrictive magnitude (-11.28 +/- 0.1 vs. -7. 02 +/- 0.9% DeltaAAD; P < 0.05, respectively). The initial AABF responses similarly exhibited similar kinetics but differing magnitudes. In contrast, during the sustained pressure input (13-97 s), the maximum vasoconstrictor magnitude (-7.02 +/- 0.9% DeltaAAD) and kinetics (-0.01% DeltaAAD/s) of the TGF-independent system were markedly blunted whereas the TGF-intact system exhibited continued vasoconstriction with slower kinetics (-0.20% DeltaAAD/s) until a steady-state plateau was reached (-25.9 +/- 0.4% DeltaAAD). Thus the TGF mechanism plays a role in both direct mediation of vasoconstriction and in modulation of the myogenic response.

Fast inhibitory signaling in the brain has conventionally been considered to be predominantly mediated by the vesicular release of GABA from presynaptic terminals onto postsynaptic GABAA receptors.1 Transient opening of such receptors results in a brief increase in postsynaptic permeability to Cl–, generating an inhibitory postsynaptic potential (IPSP) that reduces the probability of firing of the neuron. However, there is abundant evidence that GABA can also act relatively far from its site of release, and this, together with several other discoveries in the last two decades, has contributed to a reappraisal of the roles of GABAA receptors in modulating neuronal and circuit excitability.1

Our aim was to demonstrate the first use of Optically Pumped Magnetoencephalography (OP-MEG) in an epilepsy patient with unrestricted head movement. Current clinical MEG uses a traditional SQUID system for recording MEG signal, where sensors are cryogenically cooled and housed in a helmet in which the patient’s head is fixed. Here we use a different type of sensor (OPM), which operates at room temperature and can be placed directly on the patient’s scalp, permitting free head movement. We performed two 30 minute OP-MEG recording sessions in a patient with refractory focal epilepsy and compared these with clinical scalp EEG performed earlier. OP-MEG was able to identify analogous interictal activity to scalp EEG, and source localise this activity to an appropriate brain region. This is the first application of OP-MEG in human epilepsy. Future directions include simultaneous EEG/OP-MEG recording and prolonged OP-MEG telemetry.

Liu et al (Science, 304:1021-4) report that NMDA receptors containing NR2A and NR2B subunits are selectively coupled to long-term potentiation (LTP) and long-term depression (LTD) respectively. Because NR2B (but not NR2A) receptors occur outside synapses, and can be activated by glutamate spillover, this principle may underlie synaptic homeostasis.