We are interested in the role of ion channels in the neural regulation of cardiovascular and respiratory function. We investigate the role of individual channels of the neurons that compose the reflex pathways that control the activity to the heart, blood vessels and lungs using 1) patch clamp techniques for measuring the current through single ion channels, 2) imaging of intracellular calcium and membrane potential with fluorescent dyes and confocal microscopy 3) immunocytochemical localization of ion channels to specific regions of the neurons and 4) electrical recording in an isolated brainstem slice. We use this information to construct models of each of the neurons within specific reflex pathways. The models are tools used predict the transfer of information through the pathway. The goal is to understand and predict the processes that underlie plasticity and development in these pathways. A specific example of one project is our study of the involvement of ion channels in the hypertension that results from intermittent chronic hypoxia, a model for sleep apnea. In response to intermittent hypoxia, long term (but reversible) alterations in the properties of neurons in the reflex pathway lead to an increased level of sympathetic nerve activity to blood vessels and, therefore, increased blood pressure. We are uncovering hypoxia-induced changes in expression and function of specific ion channels that contribute to these alterations.

1. Glazebrook PA, Schilling WP, Kunze DL. (2005)
   TRPC channels as signal transducers. Pflugers Arch. 2005 Oct; 451(1):125-130. 2005/06/22 [aheadofprint].
   
2. Kline DD, Buniel MC, Glazebrook P, Peng YJ, Ramirez-Navarro A, Prabhakar NR, Kunze DL. (2005)
   Kv1.1 deletion augments the afferent hypoxic chemosensory pathway and respiration. J Neurosci. 2005 Mar 30; 25(13):3389-3399.
   
3. Buniel M, Wisnoskey B, Glazebrook PA, Schilling WP, Kunze DL. (2004)
   Distribution of TRPC channels in a visceral sensory pathway. Novartis Found Symp. 2004; 258:236-43; discussion 243.
   
4. Doan TN, Stephans K, Ramirez AN, Glazebrook PA, Andresen MC, Kunze DL. (2004)
   Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers. J Neurosci. 2004 Mar 31; 24(13):3335-3343.
   
5. Buniel MC, Schilling WP, Kunze DL. (2003)
   Distribution of transient receptor potential channels in the rat carotid chemosensory pathway. J Comp Neurol. 2003 Sep 22; 464(3):404-413.
   
6. Kline DD, Takacs KN, Ficker E, Kunze DL. (2002)
   Dopamine modulates synaptic transmission in the nucleus of the solitary tract. J Neurophysiol. 2002 Nov; 88(5):2736-2744.
   
7. Glazebrook PA, Ramirez AN, Schild JH, Shieh CC, Doan T, Wible BA, Kunze DL. (2002)
   Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons. J Physiol. 2002 Jun 1; 541(Pt 2):467-482.
   
8. Ramirez AN, Kunze DL. (2002)
   P2X purinergic receptor channel expression and function in bovine aortic endothelium. Am J Physiol Heart Circ Physiol. 2002 Jun; 282(6):H2106-H2116.
   
9. Doan TN, Kunze DL. (1999)
   Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons. J Physiol. 1999 Jan 1; 514 ( Pt 1):125-138.
   
10. Brosenitsch TA, Salgado-Commissariat D, Kunze DL, Katz DM. (1998)
    A role for L-type calcium channels in developmental regulation of transmitter phenotype in primary sensory neurons. J Neurosci. 1998 Feb 1; 18(3):1047-1055.
    
11. Schild JH, Kunze DL. (1997)
    Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge. J Neurophysiol. 1997 Dec; 78(6):3198-3209.
    
12. Schild JH, Clark JW, Canavier CC, Kunze DL, Andresen MC. (1995)
    Afferent synaptic drive of rat medial nucleus tractus solitarius neurons: dynamic simulation of graded vesicular mobilization, release, and non-NMDA receptor kinetics. J Neurophysiol. 1995 Oct; 74(4):1529-1548.
    
13. Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, Boyd AE 3rd. (1990)
    Ion channels and insulin secretion. Diabetes Care. 1990 Mar; 13(3):340-363.
    

1. Doan TN, Stephans K, Ramirez AN, Glazebrook PA, Andresen MC, Kunze DL. (2004)
   Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers. J Neurosci. 2004 Mar 31; 24(13):3335-3343.
   
2. Doan TN, Kunze DL. (1999)
   Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons. J Physiol. 1999 Jan 1; 514 ( Pt 1):125-138.
   
3. Koliwad SK, Elliott SJ, Kunze DL. (1996)
   Oxidized glutathione mediates cation channel activation in calf vascular endothelial cells during oxidant stress. J Physiol. 1996 Aug 15; 495 ( Pt 1):37-49.
   
4. Koliwad SK, Kunze DL, Elliott SJ. (1996)
   Oxidant stress activates a non-selective cation channel responsible for membrane depolarization in calf vascular endothelial cells. J Physiol. 1996 Feb 15; 491 ( Pt 1):1-12.
   
5. Bacal K, Kunze DL. (1994)
   Dual effects of angiotensin II on calcium currents in neonatal rat nodose neurons. J Neurosci. 1994 Nov; 14(11 Pt 2):7159-7167.
   

1. Kline DD, Takacs KN, Ficker E, Kunze DL. (2002)
   Dopamine modulates synaptic transmission in the nucleus of the solitary tract. J Neurophysiol. 2002 Nov; 88(5):2736-2744.
   
2. Ramirez AN, Kunze DL. (2002)
   P2X purinergic receptor channel expression and function in bovine aortic endothelium. Am J Physiol Heart Circ Physiol. 2002 Jun; 282(6):H2106-H2116.
   
3. Schild JH, Kunze DL. (1997)
   Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge. J Neurophysiol. 1997 Dec; 78(6):3198-3209.
   
4. Schild JH, Clark JW, Canavier CC, Kunze DL, Andresen MC. (1995)
   Afferent synaptic drive of rat medial nucleus tractus solitarius neurons: dynamic simulation of graded vesicular mobilization, release, and non-NMDA receptor kinetics. J Neurophysiol. 1995 Oct; 74(4):1529-1548.
   
5. Vaca L, Kunze DL. (1995)
   IP3-activated Ca2+ channels in the plasma membrane of cultured vascular endothelial cells. Am J Physiol. 1995 Sep; 269(3 Pt 1):C733-C738.
   
6. Vaca L, Sinkins WG, Hu Y, Kunze DL, Schilling WP. (1994)
   Activation of recombinant trp by thapsigargin in Sf9 insect cells. Am J Physiol. 1994 Nov; 267(5 Pt 1):C1501-C1505.
   
7. Vaca L, Kunze DL. (1994)
   Depletion of intracellular Ca2+ stores activates a Ca(2+)-selective channel in vascular endothelium. Am J Physiol. 1994 Oct; 267(4 Pt 1):C920-C925.
   
8. Schild JH, Clark JW, Hay M, Mendelowitz D, Andresen MC, Kunze DL. (1994)
   A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. J Neurophysiol. 1994 Jun; 71(6):2338-2358.
   
9. Hay M, Kunze DL. (1994)
   Calcium-activated potassium channels in rat visceral sensory afferents. Brain Res. 1994 Mar 14; 639(2):333-336.
   
10. Hay M, Kunze DL. (1994)
    An intermediate conductance calcium-activated potassium channel in rat visceral sensory afferent neurons. Neurosci Lett. 1994 Feb 14; 167(1-2):179-182.
    
11. Schild JH, Khushalani S, Clark JW, Andresen MC, Kunze DL, Yang M. (1993)
    An ionic current model for neurons in the rat medial nucleus tractus solitarii receiving sensory afferent input. J Physiol. 1993 Sep; 469:341-363.
    
12. Vaca L, Gurrola GB, Possani LD, Kunze DL. (1993)
    Blockade of a KCa channel with synthetic peptides from noxiustoxin: a K+ channel blocker. J Membr Biol. 1993 Jun; 134(2):123-129.
    
13. Vaca L, Kunze DL. (1993)
    Depletion and refilling of intracellular Ca2+ stores induce oscillations of Ca2+ current. Am J Physiol. 1993 Apr; 264(4 Pt 2):H1319-H1322.
    
14. Vaca L, Kunze DL. (1993)
    cAMP-dependent phosphorylation modulates voltage gating in an endothelial Cl- channel. Am J Physiol. 1993 Feb; 264(2 Pt 1):C370-C375.