Steven R Knoper
- Assistant Professor, Medicine - (Research Scholar Track)
- M.D. Medicine
- University of Washington, Seattle, Washington, United States
- B.S. Zoology
- University of Washington, Seattle, Washington, United States
- Voted Best Doctors in America: Pacific region
- Fall 1996
- Graduated cum laude from the University of Washington
- Fall 1979
- Voted Best Doctors in America
- Fall 2011
- Fall 2010
- Fall 2009
- Fall 2008
Licensure & Certification
- Medical Licensure: Arizona #16883 (1984)
- Subspecialty (1988)
- Subspecialty (2001)
- Specialty (1986)
No activities entered.
No activities entered.
- Vanderpool, R. R., Desai, A. A., Knapp, S. M., Simon, M. A., Abidov, A., Yuan, J. X., Garcia, J. G., Hansen, L. M., Knoper, S. R., Naeije, R., & Rischard, F. P. (2017). How prostacyclin therapy improves right ventricular function in pulmonary arterial hypertension. The European respiratory journal, 50(2).
- Coggan, J. S., Purnyn, S. L., Knoper, S. R., & Kreulen, D. L. (1994). Muscarinic inhibition of two potassium currents in guinea-pig prevertebral neurons: differentiation by extracellular cesium. Neuroscience, 59(2), 349-61.More infoMuscarinic responses were studied in dissociated guinea-pig celiac ganglion neurons using the whole-cell voltage-clamp technique. Muscarine (0.025-1 mM; EC50 = 95 microM) administered to cells for 1.5 s evoked inward shifts in holding current in 53 of 74 cells. The amplitude of the inward current transients decreased with hyperpolarization and the null potential averaged -71 +/- 3.4 mV (n = 11). The currents that underlie the responses to muscarine were examined with hyperpolarizing voltage stepping protocols to -100 mV from a holding potential of -30 mV. Eighty-one per cent of cells displayed voltage-dependent current relaxations characteristic of the M-potassium current. Twenty per cent of responding cells displayed no M-current but only a voltage-independent current consistent with a leak current. In the latter type of cells, the muscarine-evoked inward currents reversed near EK and became outward at more hyperpolarized potentials. Analysis of steady state I-V relationships before and after bath application of muscarine showed that the two muscarine-sensitive potassium currents were distributed differently among three types of cells: (i) with M-current (18%); (ii) with leak current (18%); and (iii) with M-current and with leak current (64%). Cesium and barium were used to differentiate the M-current and the muscarine-sensitive leak current. Barium (2 mM) reduced the M-current and the leak potassium current, whereas cesium (2 mM) reduced the M-current but did not affect leak current. Thus, barium reduced the amplitude of muscarinic responses by 79% but cesium reduced them by only 14%. We conclude that muscarinic responses in guinea-pig celiac neurons are produced by suppression of two K+ currents: the M-current and a muscarine-sensitive leak current. These two currents are differentially susceptible to the potassium channel blockers barium and cesium.
- Xian, H., Coggan, J. S., Knoper, S. R., & Kreulen, D. L. (1994). The muscarinic receptor agonist oxotremorine methiodide evokes a nicotinic response in mammalian sympathetic neurons. European journal of pharmacology, 259(1), 21-5.More infoOxotremorine methiodide, a congener of oxotremorine, is used as a muscarinic receptor agonist. Responses to oxotremorine methiodide and nicotinic receptor agonists were examined in cultured guinea-pig celiac ganglion neurons using whole-cell voltage clamp techniques. At holding potentials between -30 and -60 mV, a brief application of oxotremorine methiodide produced fast and slow inward current transients, depending upon the concentration applied. Slowly developing inward current transients, characteristic of muscarinic responses, were produced by lower concentrations (EC50: 0.3 microM) and were blocked by atropine. Rapid inward current transients, characteristic of nicotinic responses, were produced by higher concentrations of oxotremorine methiodide (EC50: 168 microM) and were blocked by d-tubocurarine. Thus oxotremorine methiodide, at concentrations of 10 microM and greater, produced an initial nicotinic fast inward current transient followed by a slow muscarinic inward transient. The fast inward transients were similar to responses evoked by the nicotinic receptor agonists acetylcholine, nicotine and 1,1-dimethyl-4-phenyl-piperazinium iodide and were not antagonized by atropine. We conclude that oxotremorine methiodide acts as a nicotinic and muscarinic receptor agonist in celiac sympathetic ganglion neurons.
- Knoper, S. R., Meehan, A. G., Purnyn, S., Coggan, J. S., Anthony, T. L., & Kreulen, D. L. (1993). CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons. European journal of pharmacology, 232(1), 65-9.More infoThe effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.
- Knoper, S. R., Matsumoto, S. G., & Kreulen, D. L. (1992). Response to 5-hydroxytryptamine on neurons of guinea pig celiac and inferior mesenteric ganglia in primary culture. Life sciences, 51(9), 703-10.More infoThe electrophysiological effects of serotonin, a putative neurotransmitter in prevertebral sympathetic ganglia, were evaluated in cultured celiac and inferior mesenteric ganglia (IMG) neurons. Intracellular microelectrode recordings were performed in neurons that were maintained in culture an average of 26 days. Seventy-eight of 85 neurons responded when serotonin (10 microM) was applied by pressure ejection from a micropipette to the surface of the isolated cells. The majority of the neurons (n = 48) generated fast depolarizations, although slow depolarizations (n = 17), bipolar responses (n = 5), hyperpolarizations (n = 7), and a biphasic response (n = 1), were also seen. Hyperpolarizing responses were evoked in celiac neurons only. All responses were inhibited by the 5-HT3 antagonist MDL 72,222 (5 microM). Fast responses were not inhibited by tetrodotoxin (n = 3). These results demonstrate that serotonin evokes a variety of membrane potential changes in cultured prevertebral sympathetic neurons by activating 5-HT3 receptors.
- Bernardo, R., Vanderpool, R., Jenkins, I., Simon, M. A., Hansen, L., Champion, H. C., Knoper, S. R., & Rischard, F. (2015, January). A concentric hypertrophic right ventricular phenotype in advanced pulmonary arterial hypertension is associated with increased ventriculo-vascular stiffening and impaired treatment response to parenteral treprostinil. 8th Pulmonary Vascular Research Institute Annual World Congress. Guangzhou, China.
- Rischard, F., Vanderpool, R., Champion, H., Simon, M., Rischard, M., Jenkins, I., Knoper, S. R., Hansen, L., & Waxman, A. (2015, January). The prospective relationship of traditional metrics of RV function to right ventriculo-vascular coupling in patients with advanced pulmonary arterial hypertension undergoing titration of parenteral treprostinil. 8th Pulmonary Vascular Research Institute Annual World Congress. Guangzhou, China.
- Rischard, F., Vanderpool, R., Champion, H., Rischard, M., Jenkins, I., Knoper, S. R., & Waxman, A. (2014, September). Afterload Reduction Governs Improvement in RV Systolic Function and Ventriculo-Arterial Adaptation in Patients with Pulmonary Arterial Hypertension(PAH) Undergoing Rapid Dose Escalation of Tresprostinil. European Respiratory Society. Munich, Germany.
- Rischard, F., & Knoper, S. R. (2013, September). Surrogate Markers of Right Ventricular Adaptation Better Predict Long-term Survival in Patients with Pulmonary Arterial Hypertension On Therapy Than Traditional Prognostic Variables. European Respiratory Society Meeting. Barcelona, Spain.
- Bernardo, R., Dalabih, M., Jenkins, I., Hansen, L., Knoper, S. R., & Rischard, F. (2015, Fall). Increased Afterload And Stroke Work During Exercise Does Not Amplify Resting Ventriculo-Vascular Uncoupling In Patients With Pulmonary Arterial Hypertension On Therapy. American Journal of Respiratory and Critical Care Medicine.
- Rischard, F., Bernardo, R., Vanderpool, R., Abidov, A., Jenkins, I., Simon, M. A., Hansen, L., Knoper, S. R., & Champion, H. C. (2015, Fall). 12. Right ventricular (RV) morphometric and ventriculo-vascular (VV) coupling patterns in patients with advanced pulmonary arterial hypertension (PAH) undergoing parenteral treprostinil therapy.
- Rischard, F., Jenkins, I., Raz, Y., Hansen, L., Thompson, J., Knoper, S. R., Hobson, N., & Hunter, K. S. (2015, Fall). RV Stroke Work Index Better Predicts Early Right Ventricular Uncoupling, Mortality, And Treatment Response Than Traditional Metrics Of Right Ventricular Function In Patients With Advanced Treatment Naive Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine.
- Hansen, L., Rischard, F., & Knoper, S. R. (2014, Fall). Right ventriculo-arterial coupling in patients with pulmonary arterial hypertension undergoing rapid dose escalation of treprostinil. Journal of Heart and Lung Transplantation.
- Knoper, S. R. (2014, April). Right ventriculo-arterial coupling in patients with pulmonary arterial hypertension undergoing rapid dose escalation of treprostinil. Journal of Heart and Lung Transplantation.
- Rischard, F., Champion, H. C., Vanderpool, R., Jenkins, I., Hansen, L., Knoper, S. R., & Waxman, A. (2014, May). Pulsatile unloading of the right ventricle results in significant afterload reduction in patients with pulmonary arterial hypertension undergoing rapid dose escalation of treprostinil. American Journal of Respiratory and Critical Care Medicine.
- Rischard, F., & Knoper, S. R. (2013, May). Surrogate Markers Of Right Ventricular Adaptation Better Predict Survival Than Does TAPSE In Patients With PAH Responding To Therapy. American Journal of Respiratory and Critical Care Medicine.
- Raz, Y., Daniel, J. C., Shah, H., Nolan, P. E., Knoper, S. R., & Moulton, M. J. (2012, September). A Three Month course of Pre-Operative Extracorporeal Membrane Oxygenation Culminating in pediatric Lung Transplantation. International Society for Heart and Lung Transplantation Annual Meeting.