by Holly R. Middlekauff, Andrea Doering, and James N. Weiss Adenosine Enhances Neuroexcitability by Inhibiting a Slow Postspike Afterhyperpolarization in Rabbit Vagal Afferent Neurons by Holly R. Middlekauff, Andrea Doering, and James N. Weiss Circulation Volume 103(9):1325-1329 March 6, 2001 Copyright © American Heart Association, Inc. All rights reserved.

Adenosine (10 μmol/L) reversibly increases action potential response rate. Adenosine (10 μmol/L) reversibly increases action potential response rate. A, Cell was stimulated at 20% threshold at 100-ms interspike intervals. At baseline, first 6 stimuli elicited action potentials, followed by hyperpolarization of cell membrane and failure to capture. B, In same cell, about 1 minute into adenosine (10 μmol/L) administration, 11 action potentials are elicited at beginning of train. Slow AHP is smaller and 6 more stimuli are followed by action potentials. C, Approximately 3 minutes into adenosine administration, slow AHP has been eliminated and there is 100% response rate to stimulus train. D, Approximately 2 minutes after washout of adenosine in same cell, first 8 stimuli elicited action potentials, followed by slow AHP and failure to capture. Dashed lines in each panel (labeled AP) show Vmax of action potentials. E, Baseline action potential response rate was 3.8±0.5%, which, after adenosine, increased to 28±7% (P=0.0009) and during washout returned to baseline levels (5±1%, P=NS). Note degree of augmentation was variable. Lines connect responses of individual neurons, open circles indicate mean±SD. Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

Forskolin (10 μmol/L) and cadmium (0 Forskolin (10 μmol/L) and cadmium (0.01 mmol/L) reversibly increase action potential response rate. Forskolin (10 μmol/L) and cadmium (0.01 mmol/L) reversibly increase action potential response rate. Left, Baseline action potential response rate was 5±1.2%, which, after forskolin, increased to 41±17% (P=0.05) and then during washout returned to baseline levels (8.5±5%, P=NS). Right, Baseline action potential response rate was 4.4±0.9%, which, after cadmium, increased to 68±17% (P=0.01) and during washout returned to baseline levels (4.6±1%, P=NS). Patch was lost in some cells before washout data could be obtained. Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

CCPA (100 nmol/L, A1-adenosine receptor agonist) did not increase action potential response rate. CCPA (100 nmol/L, A1-adenosine receptor agonist) did not increase action potential response rate. Baseline action potential response rate was 4.4±2.6%, which, after CCPA, was 9.7±4.5% (P=NS) and during washout was 7.6±3.3% (P=NS). Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

Adenosine augmentation of action potential response rate is not blocked in presence of DPCPX (5 μmol/L, A1-adenosine receptor antagonist). Adenosine augmentation of action potential response rate is not blocked in presence of DPCPX (5 μmol/L, A1-adenosine receptor antagonist). Eight cells in which adenosine reversibly increased action potential response rate (baseline, 3±1%; after adenosine, 24±9%; P=0.02) were then treated with adenosine in presence of DPCPX. Adenosine/DPCPX reversibly increased action potential response rate in these cells to similar degree as adenosine alone (baseline, 3.7±0.9%; after adenosine/DPCPX, 21±8%; P=0.02). Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

NECA (10 μmol/L, A2-adenosine receptor agonist) reversibly increases action potential response rate. NECA (10 μmol/L, A2-adenosine receptor agonist) reversibly increases action potential response rate. Baseline action potential response rate was 2.8±0.9%, which, after NECA, increased to 37±11% (P=0.02) and during washout returned to baseline levels (4.8±1.1%, P=NS). Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

Adenosine augmentation of action potential response rate is abolished in presence of ZM 241385 (10 nmol/L, A2A-adenosine receptor antagonist). Adenosine augmentation of action potential response rate is abolished in presence of ZM 241385 (10 nmol/L, A2A-adenosine receptor antagonist). Six cells in which adenosine reversibly increased action potential response rate (baseline, 3±1%; after adenosine, 27±9%; P=0.02) were then treated with adenosine in presence of ZM 241385. ZM 241385 abolished (P=0.03) increase in action potential response rate in these cells (baseline, 4±1%; after adenosine/ZM 241385, 3.5±1%). Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.

Adenosine (10 μmol/L) does not effect ICa in voltage-clamped neurons. Adenosine (10 μmol/L) does not effect ICa in voltage-clamped neurons. Summary I-V curves of ICa before and after adenosine administration in 20 nodose ganglion neurons. Holly R. Middlekauff et al. Circulation. 2001;103:1325-1329 Copyright © American Heart Association, Inc. All rights reserved.