Beta-adrenoceptor activation and PKA regulate delayed rectifier K+ channels of vascular smooth muscle cells.

Macroscopic 4-aminopyridine (4-AP)-sensitive, delayed rectifier K+ current of vascular smooth muscle cells is increased during beta-adrenoceptor activation with isoproterenol via a signal transduction pathway involving adenylyl cyclase and cAMP-dependent protein kinase (PKA) (Aiello, E. A., M. P. Walsh, and W. C. Cole. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H926-H934, 1995.). In this study, we identified the single delayed rectifier K+ (KDR) channel(s) of rabbit portal vein myocytes affected by treatment with isoproterenol or the catalytic subunit of PKA. 4-AP-sensitive KDR channels of 15.3 +/- 0.6 pS (n = 5) and 14.8 +/- 0.6 pS (n = 5) conductance, respectively, were observed in inside-out (I-O) and cell-attached (C-A) membrane patches in symmetrical KCl recording conditions. The kinetics of activation (time constant of 10.7 +/- 3. 02 ms) and inactivation (fast and slow time constants of 0.3 and 2.5 s, respectively) of ensemble currents produced by these channels mimicked those reported for inactivating, 4-AP-sensitive whole cell KDR current of vascular myocytes. Under control conditions, the open probability (NPo) of KDR channels of C-A membrane patches at -40 mV was 0.014 +/- 0.005 (n = 8). Treatment with 1 microM isoproterenol caused a significant, approximately threefold increase in NPo to 0. 041 +/- 0.02 (P < 0.05). KDR channels of I-O patches exhibited rundown after approximately 5 min, which was not affected by ATP (5 mM) in the bath solution. Treatment with the purified catalytic subunit of PKA (50 nM; 5 mM ATP) restored KDR channel activity and caused NPo to increase from 0.011 +/- 0.003 to 0.138 +/- 0.03 (P < 0. 05; n = 11). These data indicate that small-conductance, 15-pS KDR channels are responsible for inactivating the macroscopic delayed rectifier K+ current of rabbit portal vein myocytes and that the activity of these channels is enhanced by a signal transduction mechanism involving beta-adrenoceptors and phosphorylation by PKA at a membrane potential consistent with that observed in the myocytes in situ.

Imitative suicide in a cohesive organization: observations from a case study.

Three suicides occurred within 3 years in a military unit of 35 individuals. This represented an annual rate 220 times the North American average. A clinical intervention was requested by medical authorities, the goal being to minimize the risk of further deaths. Group and individual therapy was conducted over 3 days and ongoing referrals were made as necessary. In addition, measures of anxiety, depression, and hostility were obtained from this unit and from a unit equivalent in size and job description to examine whether these constructs could be used diagnostically. Analysis of the data indicated that differences in mean scores between the units yielded potentially misleading information, although on an individual basis scores were useful in identifying clients at risk of suicide. When those who personally knew one or more of the decreased were compared with those who did not, variability of scores in conjunction with interviews was helpful in identifying relatively high-risk subgroups.

Additional evidence for the relationship between Type A behavior and social support in men.

This study examined social support as a mediator of susceptibility to coronary disease in Type A individuals. Sixty-four male subjects completed the Jenkins Activity Survey and the Sarason Social Support Questionnaire. The correlations between Type A scores, the speed and impatience and hard-driving competitiveness factors of the Jenkins survey, and Sarason's social support were found to be negative, which was contrary to earlier findings. The authors hypothesize that these differing results may be a function of age and environment. Finally, and pertinent to the mechanism by which social support may be associated with coronary heart disease, systolic blood pressure was negatively correlated to satisfaction with social support.

Type A behavior, heart rate and pupillary response: effects of cold pressor and ego threat.

The present study tested the hypothesis that Type A individuals would respond to a relevant stressor (ego-threat), but not an irrelevant one (cold pressor), with higher heart rate (HR) and larger pupil size than Type B's. These measures of physiological arousal were taken during baseline and during exposure to each of two sequentially presented, but counterbalanced stress conditions: ego threat and cold pressor. The physiological measures of sympathetic arousal were supplemented with repeated measures of self-reported anxiety. Three distinct findings emerged. First, Type A subjects had higher levels of HR in response to ego threat, but lower levels in response to cold pressor stress, compared to non-stressed baseline levels. Type B's on the other hand had slight, but nondifferential increased HR to the two different stress regimens. Second, the pupillary response to light did not produce results wholly parallel to those obtained with HR, or with the hypothesis that A's are more physiologically responsive than B's. Finally the Type A subjects in all conditions reported less anxiety than did Type B's. The present results generally indicate that A/B differences in cardiovascular arousal do not generalize readily across situations or to all autonomic indices.