Intra-carotid body inter-cellular communication.

The classic peripheral chemoreflex response is a critical homeostatic mechanism. In healthy individuals, appropriate chemoreflex responses are triggered by acute activation of the carotid body - the principal chemosensory organ in mammals. However, the aberrant chronic activation of the carotid body can drive the elevated sympathetic activity underlying cardio-respiratory diseases such as hypertension, diabetes and heart failure. Carotid body resection induces intolerable side effects and so understanding how to modulate carotid body output without removing it, and whilst maintaining the physiological chemoreflex response, represents the next logical next step in the development of effective clinical interventions. By definition, excessive carotid body output must result from altered intra-carotid body inter-cellular communication. Alongside the canonical synaptic transmission from glomus cells to petrosal afferents, many other modes of information exchange in the carotid body have been identified, for example bidirectional signalling between type I and type II cells via ATP-induced ATP release, as well as electrical communication via gap junctions. Thus, herein we review the carotid body as an integrated circuit, discussing a variety of different inter-cellular signalling mechanisms and highlighting those that are potentially relevant to its pathological hyperactivity in disease with the aim of identifying novel therapeutic targets.

Recording plasticity in neuronal activity in the rodent intrinsic cardiac nervous system using calcium imaging techniques.

The intrinsic cardiac nervous system (ICNS) is composed of interconnected clusters of neurons called ganglionated plexi (GP) which play a major role in controlling heart rate and rhythm. The function of these neurons is particularly important due to their involvement in cardiac arrhythmias such as atrial fibrillation (AF), and previous work has shown that plasticity in GP neural networks could underpin aberrant activity patterns that drive AF. As research in this field increases, developing new techniques to visualize the complex interactions and plasticity in this GP network is essential. In this study we have developed a calcium imaging method enabling the simultaneous recording of plasticity in neuronal activity from multiple neurons in intact atrial GP networks. Calcium imaging was performed with Cal-520 AM labeling in aged spontaneously hypertensive rats (SHRs), which display both spontaneous and induced AF, and age-matched Wistar Kyoto (WKY) controls to determine the relationship between chronic hypertension, arrhythmia and GP calcium dynamics. Our data show that SHR GPs have significantly larger calcium responses to cholinergic stimulation compared to WKY controls, as determined by both higher amplitude and longer duration calcium responses. Responses were significantly but not fully blocked by hexamethonium, indicating multiple cholinergic receptor subtypes are involved in the calcium response. Given that SHRs are susceptible to cardiac arrhythmias, our data provide evidence for a potential link between arrhythmia and plasticity in calcium dynamics that occur not only in cardiomyocytes but also in the GP neurons of the heart.