Publications

Recent Publications (students are noted):

Merriam, L.A, Baran, C.N., Girard, B., Hardwick, J.C., May, V., and Parsons, R.L. (2013). PAC1 receptor internalization and endosomal signaling mediate the PACAP-induced increase in guinea pig neuron excitability.  Journal of Neuroscience, 6 March 2013, 33(10): 4614-4622.  View the article. 

Abstract

Following G protein-coupled receptor activation and signaling at the plasma membrane, the receptor complex often is rapidly internalized via endocytic vesicles for trafficking into various intracellular compartments and pathways.  Increasingly, the translocation of the receptor complex into signaling endosomes is recognized to be a key mechanism to produce refined and sustained intracellular signals, which may be distinct from those generated at the cell surface, for many cellular responses including growth, differentiation and survival.  Pituitary adenylate cyclase activating polypeptide (PACAP; Adcyap1) is a potent neurotransmitter/neurotrophic peptide and mediates its diverse cellular functions in part through internalization of its cognate G protein-coupled PAC1 receptor (Adcyap1r1).  In the current studies, we examined whether PAC1 receptor endocytosis participates in regulation of neuronal excitability.  While PACAP increased excitability in 90% of guinea pig cardiac neurons, whole mount preparation pretreatment with Pitstop 2 or dynasore to inhibit clathrin and dynaminI/II, respectively, suppressed the PACAP-induced increase in excitability.  Further, after the PACAP- induced action potential generation had increased, subsequent addition of inhibitor gradually attenuated excitability with no apparent changes in action potential properties.  Likewise, the PACAP-induced neuronal excitability was markedly decreased at ambient temperature.  Receptor trafficking studies with GFP-PAC1 cell lines demonstrated the efficacy of Pitstop 2 and dynasore and low temperature to suppress PAC1 receptor endocytosis.  In contrast, brefeldin A pretreatments to disrupt Golgi vesicle trafficking had no effects on PACAP-induced excitability, and PACAP/PAC1 receptor signaling still maximally increased neuronal cAMP production even with endocytic blockade.  In aggregate, these studies demonstrate that PACAP/PAC1 receptor complex endocytosis is a key step for the PACAP modulation of cardiac neuron excitability.

Jean C. Hardwick, E. Marie Southerland, Allison E. Girasole ('10), Shannon E. Ryan ('12), Sara Negrotto, and Jeffrey L. Ardell. (2012). Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease. Am J Physiol Regul Integr Comp Physiol. 2012 Nov;303(9):R950-8. doi: 10.1152/ajpregu.00223.2012. Epub 2012 Aug 29.  View the abstract here.

Michael Kerchner, Jean C. Hardwick, and Janice E. Thornton. Identifying and Using "Core Competencies" to Help Design and Assess Undergraduate Neuroscience Curricula. The Journal of Undergraduate Neuroscience Education (JUNE), Fall 2012, 11(1):A27-A37. View the PDF here.

Allison E. Girasole ('10), Christopher P. Palmer ('11), Samantha L. Corrado ('11), E. Marie Southerland, Jeffrey L. Ardell, and Jean D Hardwick (2011).  Angiotensin II potentiates adrenergic and muscarinic modulation of guinea pig intracardiac neurons.  American Journal of Physiology. 301: R1391-1399. View the abstract here.

Hardwick, J.C. and Smith, J. (2010). Undergraduate Neuroscience Faculty:  Results from a Survey of Faculty for Undergraduate Neuroscience Members. Journal of Undergraduate Neuroscience Education.8(2): A101-107.  View the PDF here.

Jean C. Hardwick, Caitlin N. Baran ('08), , E. Marie Southerland and Jeffrey L. Ardell. (2009).  Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload, American Journal of Physiology Regulatory, Integrative, and Comparative Physiology, 297: R859-R866.

Hardwick, Jean C., Baran, Caitlin N. ('08), Southerland, E. Marie, and Ardell, Jeffery L. (2009). Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload.  American Journal fo Physiology, Regulatory, Integrative, and Comparative Physiology, 297: R859-R866. 

Hardwick, Jean C., Southerland, E. Marie and Ardell, Jeffery L. (2008).  “Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus.” American Journal of Physiology, Regulatory, Integrative, and Comparative Physiology, 295: R1926-R1933.

Hardwick, J.C., Kotarski, A.F. ('04), and Powers M.J ('01). (2006) Ionic mechanisms of histamine-induced responses in guinea pig intracardiac neurons.  American Journal of Physiology, 290: R241-R250. View the abstract here.

Hardwick, Jean C. (2005). ”Preparing the Next Generation of Neuroscience Educators. “ The Journal of Undergraduate Neuroscience Education (JUNE), 3(2):E3 (Editorial). View the editorial here.

Jelson, G.S. ('02), DeMasi, G.M. ('01), Sager, K.L. ('02) and Hardwick, J.C. (2003).  Modulation of guinea pig intrinsic cardiac neurons by prostaglandins.  American Journal of Physiology 285: R682-R689.

Powers, M.J. ('01), Peterson, B.A. ('01), and Hardwick, J.C. (2001).  Regulation of parasympathetic neurons by mast cells and histamine in the guinea pig heart. Autonomic Neuroscience, 87:  37-45.

Parsons, R.L., Rossignol, T.M., Calupca, M.A., Hardwick, J.C., and Braas, K.M (2001).  PACAP peptides modulate guinea pig cardiac neuron membrane excitability and neuropeptide expression.  Annals of the New York Academy of Science, 921:  202-210.

Schoenfeld, L.K. ('99), Souder, J.A. ('02), and Hardwick, J.C. (2000).  Pituitary adenylate cyclase-activating polypeptide innervation of the mudpuppy cardiac ganglion.  Brain Research 882: 180-190.

Calupca, M.A., Hendricks, G.M., Hardwick, J.C., and Parsons, R.L (1999).  Role of mitochondrial dysfunction in the Ca2+-induced decline of transmitter release at K+-depolarized motor neuron terminals. Journal of Neurophysiology, 18:  498-506.

Braas, K.M., May, V., Harakall, S.A., Hardwick, J.C. and Parsons, R.L. (1998). PACAP modulates parasympathetic neuron excitability in guinea pig cardiac ganglia.  Journal of Neuroscience, 18: 9766-9779.

Hardwick, J.C., Mawe, G.M., and Parsons, R.L. (1997). Tachykinin-induced activation of non- specific cation conductance via NK3 neurokinin receptors in guinea-pig intracardiac neurones. Journal of Physiology, 504: 65-74.

Hardwick, J.C. and Parsons, R.L. (1996). Activation of the protein phosphatase calcineurin during carbachol exposure decreases the extent of recovery from end-plate desensitization. Journal of Neurophysiology, 76: 3609-3616.

Hardwick, J.C., Mawe, G.M, and Parsons, R.L. (1995). Evidence of afferent fiber innervation of parasympathetic neurons of the guinea-pig cardiac ganglion. Journal of the Autonomic Nervous System, 53, 166-174.