The heart
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
As in neurons, cardiac muscle cells undergo an absolute or effective refractory period in which the voltage-gated fast Na+ channels become inactivated at the peak of the action potential and are incapable of opening regardless of further stimulation. Therefore, the fast Na+ channels cannot reopen, Na+ ions cannot enter the cell, and another action potential cannot be generated. These channels do not return to their resting position and become capable of opening in sufficient numbers to generate a new action potential until the cardiac muscle cell has repolarized to approximately −70 mV. The absolute refractory period lasts almost as long as the duration of the associated contraction, about 250–300 ms. The physiological significance of this phenomenon is that it prevents the development of tetanus or spasm of the ventricular myocardium. By the time the cardiac muscle cell can be stimulated to generate another action potential, the contraction from the previous action potential is over. Therefore, the tension from sequential action potentials cannot accumulate and become sustained. This contrasts with skeletal muscle where tetanic contractions readily occur to produce maximal strength (Chapter 12). The pumping action of the heart, however, requires alternating contraction and relaxation so that the chambers can fill with blood. Sustained contraction or tetanus would preclude ventricular filling.
Pharmacological diagnostic tests
Harald Breivik, William I Campbell, Michael K Nicholas in Clinical Pain Management, 2008
Nerve injury is associated with a reduction of some sodium channels and the development of novel sodium channels (downregulation of Nav1.8 and Nav1.9 sodium channels is associated with slow tetrodotoxin-resistant currents; up-regulation of Nav1.3 sodium channels is associated with fast tetrodotoxin-sensitive currents). There is also a change in the distribution of these channels (with an increase in cell body, dendrites, and tips of injured axons). The consequences of these changes are that injured cutaneous afferents become prone to generating more prolonged and higher frequency discharges. The refractory period is reduced. These changes in the characteristics of sodium channels are thought to underlie the mechanisms of mechanosensitivity, thermosensitivity, and chemosensitivity.6 Recent data show that local anesthetics may also have pain-relieving actions via targets other than sodium channels, including neuronal G protein-coupled receptors and binding sites on immune cells.7
Atrial fibrillation and other arrhythmias
Neeraj Parakh, Ravi S. Math, Vivek Chaturvedi in Mitral Stenosis, 2018
Pathological changes in atria results in marked alteration in their electrophysiological properties. Electrophysiological study of atria in patients undergoing percutaneous transvenous mitral commissurotomy (PTMC) revealed significant abnormalities. There are low-voltage and no-voltage signals indicating electrical scarring. Local and global conduction abnormalities in the form of fractionated electrograms, double potentials, and increased conduction time are present. The effective refractory period is either normal or increased. On electrical stimulation, these patients have a higher tendency to develop atrial fibrillation. These abnormalities were present in both atria, with the LA being affected more than the RA.34 Chronic atrial stretch also leads to direction-dependent conduction slowing and anisotropy leading to a fertile substrate for the development of atrial fibrillation.35 Mitral valvotomy in MS with AF reduces electrical anisotropy of the effective refractory period in the LA but atrial conduction properties remain unchanged.36
Changes in nerve excitability indices in hereditary transthyretin amyloidosis
Published in Amyloid, 2019
Taro Yamashita, Mitsuharu Ueda, Sonoko Misawa, Yasuteru Inoue, Teruaki Masuda, Yohei Misumi, Kotaro Takamatsu, Konen Obayashi, Satoshi Kuwabara, Yukio Ando
The strength duration time constants (SDTCs) in patients with ATTRm amyloidosis (mean 0.43 ± 0.10, median 0.41, range 0.18–0.51) tended to be shorter than those in control subjects (mean 0.48 ± 0.07, median 0.48, range 0.41–0.57) (reduced excitability, decreased persistent sodium current) (Figure 1(A,C,D)). The slope of the curve for threshold change versus stimulus width (rheobase) in the patients tended to be higher than that in control subjects (reduced excitability) (Figure 1(A)). The threshold reduction in hyperpolarizing threshold electrotonus (TE) in the patients tended to be larger than that in control subjects (fanning out, increased threshold, hyperpolarization; S2 phase: abnormal slow potassium channel, hyperactivity of the sodium–potassium pump) (Figure 1(B)). The SDTCs in patients with ATTRm amyloidosis were weakly and inversely correlated with the duration of disease (Figure 1(C)). The hyperpolarizing current–threshold (I/V) slope in motor axons in the patients tended to be higher than that in control subjects (Figure 1(E)). The relative refractory period of the patients was prolonged compared with that of controls (Figure 1(F)).
Challenging the Standard Model of Sexual Response: Evidence of a Variable Male Sexual Response Cycle
Published in The Journal of Sex Research, 2020
Dean M. Busby, Nathan D. Leonhardt, Chelom E. Leavitt, Veronica Hanna-Walker
Even though the lack of a distinction between the arousal and desire constructs for men was consistent with the findings from previous studies on women and their sexual response cycles (Basson, 2008; Leavitt, Leonhardt, et al., 2019), the findings from the current study are distinct. The most important distinction between the two genders is that in this study the lowest arousal group was still in a medium range, whereas in Leavitt, Leonhardt, et al.’s 2019’s study (2019) 8% of the sample of women were in a very low arousal group that had substantially lower scores on all outcome measures. The other difference noted in the patterns of arousal between men in this study and women in Leavitt, Leonhardt, et al.’s study (2019) is that men in general had a more substantial drop in arousal at the end of their experience than women, verifying the reality of a refractory period for them (Seizert, 2018).
Biological therapies targeting arrhythmias: are cells and genes the answer?
Published in Expert Opinion on Biological Therapy, 2018
Debbie Falconer, Nikolaos Papageorgiou, Emmanuel Androulakis, Yasmin Alfallouji, Wei Yao Lim, Rui Providencia, Dimitris Tousoulis
Atrioventricular Nodal Re-entrant Tachycardia is also caused by a re-entrant mechanism. It occurs secondary to the presence of two pathways within the atrioventricular node (AVN) which have different electrophysiological properties. It occurs as the fast pathway that exists has rapid conduction and a longer refractory period in comparison to the AVN, creating a substrate for re-entry. The impulse will travel through both pathways in normal conditions. In the presence of a premature stimulate, the stimulus blocks in the faster pathway due to a longer refractory period and travels through the slower accessory pathway. If slow enough, the blocked pathway can have time to recover, setting the state for re-entry. In response to a premature stimulation, the stimulus can block the fast pathway due to a longer refractory period and travel through the slow pathway. If conduction is slow enough, the blocked fast pathway can have time to recover, thus setting the stage for a re-entrant circuit, translating into atrioventricular nodal tachycardia (AVRT) when perpetuated.
Related Knowledge Centers
- Action Potential
- Physiology
- Autowave
- Excitable Medium
- Neuron
- Voltage-Gated Potassium Channel
- Autowave Reverberator