A B S T R A C T The origin and regulatory mechanisms of tonic tension (Ca currentindependent component of contractility) were investigated in frog atrial muscle under voltage-clamp conditions. Tonic tension was elicited by depolarizing pulses of 160 mV (Em = +90 mV, i.e., close to E ca) and 400-600 ms long. An application of Na-free (LiCI) or Ca-free Ringer's solutions resulted in a fast (<120 s), almost complete abolition of tonic tension. When [Na]0 was reduced (with LiCI or sucrose as the substitutes), the peak tonic tension increased transiently and then decreased below the control level. The transient changes in tonic tension were prevented by using low-Na, low-Ca solutions where the ratios [Ca]d[Na]o 4 to [Ca]d[Na]o 4 were kept constant (1.1 x 10 -s mM -a to 8.7 x 10 -la mM-5). Na-free (LiCl) solution elicited contractures accompanied by a membrane hyperpolarization or by an outward current even when the Na-K pump was inhibited. 15 mM MnCl2 (or 3 mM LaCla) inhibited the development of the Na-free contracture and the related part of hyperpolarization or the outward current. In conclusion, our results indicate that tonic tension is regulated by a Na-Ca exchange mechanism. Furthermore, they suggest that this exchange could be electrogenic (exchanging three or more Na ions for one Ca ion) and thus voltage dependent. The possible contribution of an electrogenic Na-Ca exchange in the maintenance of cardiac membrane potential is discussed.

Functional data indicate that neurons in distinct regions of the heart exert preferential regional cardiac control. To date the regional distribution of specific types of neurons within the intrinsic cardiac nervous system remains unknown, as does their associations with distinct neurotransmitter and/or neuromodulatory profiles. This study was designed to ascertain: (1) the distribution of different classes of neurons within the intrinsic cardiac nervous system as determined by microscopic analysis; (2) the neurochemical profiles of neurons in differing atrial loci; (3) which neurochemicals are co-localized within specific populations of intrinsic cardiac neurons; and (4) the distribution of specific sub-populations of neurons expressing specific immunoreactivities. Taking advantage of confocal laser scanning microscopy and distinct immunoreactive fluorescent markers in various double-label combinations, several sub-populations of intrinsic cardiac neurons were identified. Of all identified neurons, 85-90% were located in ganglia (ganglionic neurons), the rest being isolated (individual neurons). The two general neuronal markers protein gene product 9.5 (PGP 9.5) and microtubule-associated protein (MAP-2) were associated with neurons clustered primarily in the interatrial septum and around the origins of the two vena cavae. Ganglia (group 1) contained three sub-populations of neurons: approx. 80% of ganglionic neurons were large (15-40 microm diameters; group 1a) and approx. 20% had smaller diameters (less than 15 microm; group 1b). All of these neurons were PGP-immunoreactive, exhibiting choline acetyltransferase (ChAT) immunoreactivity (IR), tyrosine hydroxylase (TH) IR, neuropeptide Y (NPY) IR, vasoactive peptide (VIP) IR and substance P (SP) IR. The remaining 5% of ganglionic neurons were small (group 1c; less than 20 microm). These displayed TH immunoreactivity but not MAP, PGP, CHAT, NPY or SP immunoreactivity. Ten to fifteen percent of all neurons loosely distributed outside of ganglia were small (10-25 microm) and located primarily around the origin of the superior vena cava. They displayed immunoreactivity to TH, ChAT, VIP, NPY and SP, but not to MAP-2 or PGP 9.5. These data provide anatomical and immunohistochemical evidence for specific localization of differing populations of intrinsic cardiac neurons with respect to their size, ganglionic distributions and capacity to express multiple neurotransmitters. Although the functional importance of such a regional distribution of differing populations of intrinsic cardiac neurons remains unknown, these anatomical data support the thesis that unique clustering of specific populations of neurons within this nervous system represents the anatomical substrate for complex local cardiac regulatory phenomena occurring at the level of the target organ.

The data indicate that SIH provides a very powerful and very fast protection against the oxidative stress exerted by H(2)O(2) presumably via the iron-mediated Fenton reaction producing hydroxyl radical (OH), whereas the protective effect of DFO is hindred by its very slow and rather limited intracellular entry, and the protection that MIA exerts via the inhibition of Na(+)/H(+) exchange against H(2)O(2) much less effective.

No abstract

To determine the chemotransduction characteristics of ventricular sensory neurites associated with nodose ganglion afferent neurons, various chemicals were applied individually to epicardial sensory neurites associated with individual afferent neurons in anesthetized guinea pigs. The following ion channel-modifying agents were tested: barium chloride, cadmium chloride, calcium chloride, the chelating agent EGTA, nickel chloride, potassium chloride, tetraethylammonium chloride, and veratridine. An acidic solution (pH 6.0) and oxygen-derived free radicals (H(2)O(2)) were tested. The following chemicals were also tested: adenosine, alpha- and beta-adrenergic agonists, angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), histamine, nicotine, the nitric oxide donor nitroprusside, substance P, and vasoactive intestinal peptide. A total of 102 cardiac afferent neurons was identified, of which approximately 66% were sensitive to mechanical stimuli applied to their epicardial sensory fields. Application of individual ion channel-modifying agents to epicardial sensory fields modified most associated afferent neurons, with barium chloride affecting each neuron studied. Ventricular sensory neurites associated with most identified neurons were also responsive to the other tested chemicals, with hydrogen peroxide, adenosine, angiotensin II, bradykinin, CGRP, clonidine, and nicotine inducing responses from at least 75% of the neurons studied. It is concluded that 1) the ventricular sensory neurites associated with nodose ganglion afferent neurons transduce a much wider variety of chemical stimuli than considered previously, 2) these sensory neurites employ a variety of membrane ion channels in their transduction processes in situ, and 3) adrenergic agents influence on sensory neurites associated with cardiac afferent neurons suggests the presence of a cardiac feedback mechanism involving local catecholamine release by adjacent sympathetic efferent postganglionic nerve terminals.