Is Impaired Baroreflex Sensitivity a Predictor or Cause of Sudden Death in Insulin-dependent Diabetes Mellitus?

Lawrence, Ian; Weston, PJ; Bennett, M.A.; McNally, PG; Burden, A C; Thurston, H.

doi:10.1002/(sici)1096-9136(199701)14:1<82::aid-dia290>3.0.co;2-3

Cited by 33 publications

(19 citation statements)

References 2 publications

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“…Therefore, the NA plays a key role in arterial baroreflex control of heart rate. Impairment of arterial baroreflex function has been used as an indicator of potential life-threatening arrhythmia and heart failure (13,34). Despite this, little is known concerning the cellular mechanisms responsible for the alteration of membrane properties and neuronal activity of PCMNs, which may underlie the dysfunction of arterial baroreflex in disease states.…”

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confidence: 99%

Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Lin

Hatcher

Wurster

et al. 2014

American Journal of Physiology-Cell Physiology

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Large-conductance Ca2(+)-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca(2+)-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+]50 was 15.2 μM with a P0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (IAHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability.

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confidence: 99%

Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Lin

Hatcher

Wurster

et al. 2014

American Journal of Physiology-Cell Physiology

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“…In many cardiovascular diseases (e.g., diabetes and chronic intermittent hypoxia as a model for sleep apnea and aging), baroreflex sensitivity is reduced (23,24,35,37,68,69). Impairment of baroreflex has been used as an indicator of potential lifethreatening arrhythmia and heart failure (14,30). Therefore, it is very important to study the action potential (AP) firing properties and excitability of PCMNs, as well their underlying mechanisms under normal conditions.…”

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confidence: 99%

Small conductance Ca²⁺-activated K⁺channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Lin

Hatcher

Chen

et al. 2010

American Journal of Physiology-Cell Physiology

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Small conductance Ca(2+)-activated K(+) channels (SK) regulate action potential (AP) firing properties and excitability in many central neurons. However, the functional roles of SK channels of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal days 7-9. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. With the use of whole cell current clamp, single APs and spike trains of different frequencies were evoked by current injections. We found that 1) PCMNs have two different firing patterns: the majority of PCMNs (90%) exhibited spike frequency adaptation (SFA) and the rest (10%) showed less or no adaptation; 2) application of the specific SK channel blocker apamin significantly increased spike half-width in single APs and trains and reduced the spike frequency-dependent AP broadening in trains; 3) SK channel blockade suppressed afterhyperpolarization (AHP) amplitude following single APs and trains and abolished spike-frequency dependence of AHP in trains; and 4) SK channel blockade increased the spike frequency but did not alter the pattern of SFA. Using whole cell voltage clamp, we measured outward currents and afterhyperpolarization current (I(AHP)). SK channel blockade revealed that SK-mediated outward currents had both transient and persistent components. After bath application of apamin and Ca(2+)-free solution, we found that apamin-sensitive and Ca(2+)-sensitive I(AHP) were comparable, confirming that SK channels may contribute to a major portion of Ca(2+)-activated K(+) channel-mediated I(AHP). These results suggest that PCMNs have SK channels that significantly regulate AP repolarization, AHP, and spike frequency but do not affect SFA. We conclude that activation of SK channels underlies one of the mechanisms for negative control of PCMN excitability.

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“…Also, in patients affected by myocardial infarction [44] and diabetes mellitus [45], pressure-derived BRS offers prognostic value for non-sustained ventricular tachycardia and sudden cardiac death. The question remains whether the vulnerable subgroup of myocardial and diabetic patients has lower arterial wall stiffness or a decrease in the sensing and neural components of the baroreflex.…”

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confidence: 99%

Neural activity of the cardiac baroreflex decreases with age in normotensive and hypertensive subjects

Kornet

et al. 2005

Journal of Hypertension

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Is Impaired Baroreflex Sensitivity a Predictor or Cause of Sudden Death in Insulin-dependent Diabetes Mellitus?

Cited by 33 publications

References 2 publications

Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Small conductance Ca²⁺-activated K⁺channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Neural activity of the cardiac baroreflex decreases with age in normotensive and hypertensive subjects

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Is Impaired Baroreflex Sensitivity a Predictor or Cause of Sudden Death in Insulin-dependent Diabetes Mellitus?

Cited by 33 publications

References 2 publications

Characteristics of single large-conductance Ca2+-activated K+channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Characteristics of single large-conductance Ca2+-activated K+channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Small conductance Ca2+-activated K+channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Neural activity of the cardiac baroreflex decreases with age in normotensive and hypertensive subjects

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Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Characteristics of single large-conductance Ca²⁺-activated K⁺channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

Small conductance Ca²⁺-activated K⁺channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus