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Presynaptic stimulus-release and postsynaptic compensatory changes in mice lacking the N-type calcium channel
Natalia N Petrashevskaya1, Masakazu Ishii, Karen D'Souza
1Institute of Molecular Pharmacology and Biophysics, Department of Surgery, University of Cincinnati College of Medicine, OH 45267-0828, United States. petrashevskayn@mail.nih.gov
Autonomic Neuroscience : Basic & Clinical
|October 13, 2010
Summary
Ablation of N-type (Ca(v)2.2) voltage-dependent calcium channels reduced sympathetic stimulation effects on the heart. However, parasympathetic responses remained unchanged, and α(1)-adrenergic stimulation showed an increased contractile response.
Area of Science:
- Cardiovascular Physiology
- Neuropharmacology
- Autonomic Nervous System Regulation
Background:
- N-type (Ca(v)2.2) voltage-dependent calcium channels (VDCC) are crucial for neurotransmitter release in the autonomic nervous system.
- These channels are potential therapeutic targets for cardiovascular diseases.
- Understanding the role of N-type VDCC in cardiac function and autonomic regulation is clinically significant.
Purpose of the Study:
- To investigate the physiological impact of N-type VDCC ablation on cardiac function.
- To examine the effects on stimulus-release coupling and cardiac autonomic regulation.
- To determine the consequences of N-type channel deficiency on sympathetic and parasympathetic nervous system activity in the heart.
Main Methods:
- Utilized mice genetically deficient in the α(1B) subunit of the N-type channel (N-type-/-).
- Assessed cardiac function using high-frequency field stimulation (HFFS) to evaluate inotropic responses.
- Measured postsynaptic β-adrenergic responsiveness, β-adrenoreceptor density, adenylyl cyclase activity, and α(1)-adrenoreceptor (α(1)-ADR) stimulation response.
Main Results:
- N-type-/- mice showed a significant decrease (33%) in the positive inotropic effect from sympathetic stimulation compared to Wild-Type (89%).
- Negative inotropic responses mediated by parasympathetic stimulation were similar in N-type-/- and WT mice.
- N-type-/- hearts exhibited an enhanced contractile response to α(1)-ADR stimulation, potentially due to increased PLCβ1 expression.
Conclusions:
- Selective impairment of sympathetic nervous system inflow via N-type VDCC does not alter postsynaptic β-adrenergic responsiveness.
- The study suggests an increased functional response to α(1)-adrenergic stimulation in the absence of functional N-type channels.
- These findings highlight the specific role of N-type VDCC in sympathetic neurotransmission and cardiac contractility modulation.
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